Hormone and Appetite During Puberty Paper
Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathological weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety.Hormone and Appetite During Puberty Paper Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.
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Before your body can benefit from any nutrients you consume, your gastrointestinal tract has to digest and absorb the foods you eat. But before you eat, it helps to feel hungry.
Hunger is the feeling you get when your body needs food. When you’ve had enough to eat, you shouldn’t feel hungry anymore. That’s because a variety of hormones regulate hunger:
Leptin. A hormone secreted by adipose tissue (fat) into your bloodstream. The more fat on your body the higher your blood levels of leptin. Your leptin level also increases with food intake and is higher in females than males, but overall, it gets lower as you get older. Increased leptin levels trigger the hypothalamus to reduce hunger.
Ghrelin. A hormone produced by the stomach and small intestine when your stomach is empty. Like leptin, it also works with the hypothalamus, but instead of suppressing hunger, it increases hunger.
Adiponectin. A hormone secreted by fat cells in your body. But as your level of body fat goes down, this hormone goes up and vice versa; when you gain fat, your adiponectin levels go down.
Cholecystokinin. This hormone is produced in the small intestine during and after a meal. It triggers the release of bile and digestive enzymes into the small intestine, and it suppresses hunger and makes you feel full.
Peptide YY. Made by both the large and small intestine after a meal, this hormone suppresses your appetite for about 12 hours after you eat.
Insulin. The pancreas produces this hormone. It’s best known for regulating blood sugar levels. It also suppresses hunger.
Glucocorticoids. These hormones are made by your adrenal glands, and their primary function is to regulate inflammation and other processes, but they also have an impact on hunger. A cortisol deficiency reduces appetite, but excessive amounts of glucocorticoids increase hunger.Hormone and Appetite During Puberty Paper
Hunger vs. Appetite
Hunger isn’t the same as appetite. Appetite is one reason why you can eat so much when you’re not hungry.
Hunger is a physical reaction caused by hormonal and chemical changes in your body when you need more food. Appetite is more psychological in nature and is sometimes a learned response to certain foods.
Now that you’re hungry, it’s time to eat. Digestion is coordinated and regulated by several hormones:
Gastrin. A hormone released by the stomach and the small intestine when you eat. Gastrin stimulates the release of hydrochloric acid and pepsinogen in the stomach, and it speeds up digestion. Also, gastrin stimulates glucagon, a hormone that works with insulin to regulate blood sugar.
Secretin. A hormone made by the small intestine and secreted into the bloodstream when the acidic chyme from the stomach enters the small intestine. Secretin stimulates the pancreas to release bicarbonate-rich digestive juices into the small intestine. The bicarbonate neutralizes the acidity of the chyme. Secretin acts on the stomach to trigger production of pepsinogen to help break down proteins, and it might also slow down the digestive process, at least in the area of the stomach and first part of the small intestine.Hormone and Appetite During Puberty Paper
Cholecystokinin (CCK). Your small intestine makes and releases CCK into your bloodstream. It’s essential for fat digestion because it stimulates the gallbladder to release bile into the small intestine. It also triggers the pancreas to release its various digestive enzymes into the small intestine so they can break down fats, carbohydrates, and proteins.
Motilin. Another hormone made by the small intestine. Motilin speeds up activity in the stomach and small intestine. It also stimulates the stomach and pancreas to release various secretions and causes the gallbladder to contract.
Glucose-dependent insulinotropic peptide (GIP). This hormone is made by the small intestine. It stimulates the pancreas to release insulin and slows down digestive activity in the stomach. This hormone is sometimes called gastric inhibitory peptide.
Understanding body weight regulation will aid in the development of new strategies to combat obesity. This review examines energy homeostasis and food intake behaviors, specifically with regards to hormones, peptides, and neurotransmitters in the periphery and central nervous system, and their potential role in obesity.Hormone and Appetite During Puberty Paper Dysfunction in feeding signals by the brain is a factor in obesity. The hypothalamic (arcuate nucleus) and brainstem (nucleus tractus solitaris) areas integrate behavioral, endocrine, and autonomic responses via afferent and efferent pathways from and to the brainstem and peripheral organs. Neurons present in the arcuate nucleus express pro-opiomelanocortin, Neuropeptide Y, and Agouti Related Peptide, with the former involved in lowering food intake, and the latter two acutely increasing feeding behaviors. Action of peripheral hormones from the gut, pancreas, adipose, and liver are also involved in energy homeostasis. Vagal afferent neurons are also important in regulating energy homeostasis. Peripheral signals respond to the level of stored and currently available fuel. By studying their actions, new agents maybe developed that disable orexigenic responses and enhance anorexigenic signals. Although there are relatively few medications currently available for obesity treatment, a number of agents are in development that work through these pathways.
According to endocrinologists from the VU University Medical Center in Amsterdam, two of the most important hormones to focus on for natural weight loss and energy balance are ghrelin and leptin. (1) Many experts call ghrelin and leptin the “hunger hormones” because they work to either increase or decrease our appetite. (2)Hormone and Appetite During Puberty Paper
Although certain weight loss programs involving taking artificial hormones — such as those that use human chorionic gonadotropin (HCG) to increase fat-burning — can be dangerous, there are safe and effective steps we can take to manipulate our natural hunger hormones and help us reach our weight-loss goals.
It might feel like the cards are stacked against you when it comes achieving sustainable weight loss, but it’s important to understand that we have a great deal of control over our hormones, as they reliably respond to dietary, exercise and stress-related changes we make. We don’t need to resort to unnatural, harmful methods to lose weight fast and reach our ideal weight — instead we need to focus on setting up a healthy food environment that encourages nutrient-dense eating, managing stress, moving our bodies consistently and making smart food choices long-term.
What Is Ghrelin?
Ghrelin is an appetite-increasing hormone, given its name because it is considered to be a “growth hormone-releasing peptide” (or GHR). Since ghrelin makes you feel hungry, it makes sense that levels tend to rise before meals and fall after meals. How is ghrelin secreted? It’s made in the stomach and fluctuates throughout the day depending on your intake of food. As a peptide hormone, it’s produced by ghrelinergic cells located in the gastrointestinal tract, which communicate with the central nervous system, especially the brain.
Once produced in the stomach, rising levels of ghrelin sends a signal to the brain that causes you to feel hungrier. Regarded as the only appetite-stimulating hormone in humans, ghrelin is one of the main contributors in giving people the “munchies” and potentially causing them to overeat.Hormone and Appetite During Puberty Paper
What is ghrelin’s effect on growth hormone and metabolism?
Ghrelin and related growth hormone secretagogues increase body weight and fat mass. One way they do this is by triggering receptors in a part of the brain called the arcuate nucleus, which controls leptin and insulin sensitivity. Ghrelin can sometimes override signals sent from the GI tract to the brain that tells you to stop eating, such as those caused by gastric distension (pressure placed on the stomach as it expands). Ghrelin also seems capable of contributing to cellular changes, including alterations in endothelial cells lining the blood vessels. (3)
According to research published in the journal Addiction Biology, ghrelin reduces fat utilization and is a vital component of the food reward cascade controlled by the brain’s pleasure-reward system. (4) Ghrelin levels are negatively correlated with weight, so dieting (especially severe calorie restriction) tends to increase ghrelin output. Ghrelin has been found to play a major role in inducing short-term feeding and long-term weight gain, but the hormone also has other roles, including influencing: (5)
Regulation of growth hormone and insulin secretion
Glucose and lipid metabolism
Blood pressure and heart rate
And neurogenesis (the process in which neurons are generated from neural stem cells)Hormone and Appetite During Puberty Paper
In addition, more ghrelin is released directly in response to stressful situations, explaining why so many people have the tendency to eat when they’re stressed. By perpetuating the stress cycle, ghrelin contributes to weight gain by maintaining a person’s stress levels and causing strong urges to snack or overeat.
Nutrition is one of the most important factors affecting pubertal development. Puberty entails a progressive nonlinear process starting from prepubescent to full sexual maturity through the interaction and cooperation of biological, physical, and psychological changes. Consuming an adequate and balanced healthy diet during all phases of growth (infancy, childhood and puberty) appears necessary both for proper growth and normal pubertal development. Girls begin puberty at an earlier age compared to past decades. Excessive eating of many processed, high-fat foods, may be the cause of this phenomenon. Overweight or obese children are more likely to enter puberty early. Some evidence suggests that obesity can accelerate the onset of puberty in girls and may delay the onset of puberty in boys. Moreover, the progression of puberty is affected by nutrition. On the other hand, puberty triggers a growth spurt, which increases nutritional needs including macro and micro nutrients. Increased caloric, protein, iron, calcium, zinc and fol ate needs have to be provided during this critical period of rapid growth. Severe primary or secondary malnutrition also can delay the onset and progression of puberty. The higher incidence of anorexia nervous and bulimia in adolescents imposes a nutritional risk on pubertal development. Moreover, many environmental endocrine disruptions (EDs) have been identified that can significantly impair the normal course of puberty. This mini-review sums up some important findings in this important complex that link nutrition and pubertal development.Hormone and Appetite During Puberty Paper
Puberty marks the entry of a child into adolescence and sexual maturity. During puberty, your body goes through many changes that affect the way you look, feel and behave. Eating a healthy diet affects the age at which you reach puberty as well as your growth during puberty. Talk to your doctor about your eating habits to make sure they keep you healthy during this important time of growth.
A series of hormonal changes triggers the production of luteinizing hormone and follicle-stimulating hormone, which begin changes in your body. Boys and girls enter a growth spurt in which they get taller and experience redistribution of weight on their bodies. Young men begin producing testosterone and adult sperm cells. The eggs in a young woman’s ovaries begin to mature and she produces estrogen. These physiological changes mark your movement toward sexual maturity.
Age of Onset
The age of onset of puberty depends on a variety of factors, including nutrition. Most girls enter puberty between age 8 and 13, while guys enter puberty from age 10 to 15. A 2010 study published in “Pediatrics” by Frank Biro found that girls begin puberty at a younger age than in previous decades. The modern American diet, which includes many processed, high-fat foods, may be to blame for this phenomenon. Being overweight or obese increases the likelihood that a girl will enter puberty earlier than average. Obesity may delay the onset of puberty in boys.
Research presented at the 2008 annual meeting of the Endocrine Society by scientist Deborah Sloboda found that pregnant rats that ate a high-fat diet had babies that reached puberty sooner. This suggests that a mother’s prenatal diet may affect her child’s age of pubertal onset.Hormone and Appetite During Puberty Paper
In addition to affecting the age of pubertal onset, nutrition affects a child’s progression through puberty. Puberty triggers a growth spurt, which increases your daily caloric needs. Following a healthy diet helps your body grow without becoming overweight. An adolescent also needs more protein, iron, calcium, zinc and fol ate during puberty for healthy growth. Menstruating girls are at an especially high risk of iron deficiency. Failing to get enough calcium or protein during puberty may damage your bone and muscle growth, which could affect your health later in life.
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In addition to delaying the onset of puberty, being overweight could cause hormonal imbalances that lead to serious health problems. Maintaining a healthy diet before and during puberty is essential to proper growth and development. Other factors, including genetics and environmental agents, also affect pubertal onset and development. Talk to your doctor about your diet to make sure you get enough nutrients during puberty.
What if we could, for one day, create our bodies and change them as we please to improve our physical nature? How would we enhance our strengths and address what we see as problems? How would we change our bodies and minds to alleviate stress, anxiety and physical problems? Related to weight, we would probably make it easier and very straightforward to lose pounds and fat and to keep the weight off our bodies.Hormone and Appetite During Puberty Paper
If we had this power, we might consider simplifying hormonal actions that fuel and curb hunger so these actions are clear-cut and we comprehend exactly how to lose weight. In fact, in real life, two hormones do appear to be this direct in their actions on eating and weight. Ghrelin (grell-in) is the hunger hormone and leptin is the stop appetite hormone. Many believe that the actions of these “go and stop” appetite hormones are straightforward, and that one is bad and the other is good.
Ghrelin, the “Hunger Hormone”
Ghrelin is responsible for stimulating hunger, and it is the “go” hormone that tells you when to eat. As the “hunger hormone,” some may be ready to make ghrelin out to be a villain. Obesity and weight-loss are complicated, so perhaps it would be comforting to have a bad guy hormone that stimulates hunger so we can focus on this “bad” hormone that causes us to gain weight.
What exactly is meant by saying ghrelin is the hunger hormone? The ghrelin hormone, discovered in 1999, is released primarily from cells in the stomach and travels to the brain. There, it interacts with both the hypothalamus (the brain’s physiological eating center) and the brain’s pleasure centers to arouse hunger.Hormone and Appetite During Puberty Paper
Throughout the course of a day, ghrelin levels naturally change dramatically, rising steeply before a meal and then plummeting after eating. Ghrelin stimulates the brain, which leads to an increase in appetite, and it slows metabolism and decreases the body’s ability to burn fat. Ghrelin also favors the amassing of fatty tissue in the abdominal area. In experiments, people who got injections of ghrelin before a buffet meal ate 30 percent more than a group of eaters not given extra ghrelin.
Like many things in life, it is not as apparent as it seems that ghrelin is a hunger hormone and therefore bad. Consider, for example, that ghrelin levels in the blood of individuals affected by obesity are lower than those in leaner individuals. That finding is opposite to expectations that obesity would be due to excess levels of the hunger hormone. It has also been discovered that individuals suffering from anorexia have high blood levels of ghrelin compared to both the thin and normal-weight controls.
The findings suggest that ghrelin is inversely related to calorie intake. Other studies have found that individuals who lose weight and try to keep it off make more ghrelin than they did before losing weight, as if their bodies are fighting to regain the lost fat. An explanation for these findings is that excess weight may increase sensitivity to ghrelin. For example, there may be more receptors in those affected by obesity for the hormone, so not as much ghrelin is needed to stimulate hunger.Hormone and Appetite During Puberty Paper
Leptin, the “Stop Appetite Hormone”
The opposing hormone to ghrelin is the stop appetite hormone, leptin. Leptin is a hormone produced in the fat cells. It plays a role in regulating body weight by signaling the brain to reduce appetite and burn more calories. Leptin is a primary modulator of body weight and metabolism, and it mediates weight-loss by decreasing hunger and food consumption and increasing energy expenditure. Yet, some studies have shown that losing weight causes a marked decrease in leptin levels, which may in turn increase appetite.
Counter to what would be anticipated, obesity is linked to unusually high concentrations of leptin. Some research suggests that these high concentrations make the receptors for leptin inactive and impair the very mechanism that should eliminate excess fat. Then, although plenty of leptin is produced, the body’s appetite suppression system is unable to function properly.
Ghrelin Blockers as a Weight-loss Treatment
If ghrelin stimulates hunger, wouldn’t a ghrelin inhibitor (antagonist) be effective in helping people lose weight? Several pharmaceutical companies have or are conducting research on such a compound. The Scripps Research Institute in California in 2006 successfully developed an anti-obesity ghrelin vaccine that significantly slowed weight gain and reduced body fat in animals. It is possible that in the future there will be a ghrelin blocking medication. But, since ghrelin also makes eating food more pleasurable, a drug blocking the brain’s pleasure centers might create side effects related to mood regulation.Hormone and Appetite During Puberty Paper
The research on ghrelin blockers is no slam dunk. Take as an example the promising medication, rimonabant, which works by interfering with one of the brain’s cannabinoid receptors and successfully causes weight-loss. However, rimonabant also affects the pleasure center in the brain and side effects include the potential for severe depression, sometimes leading to suicide. This drug was not approved for use due to these side effects.
Finally, what is not known is how important the role ghrelin plays in everyday eating and weight gain/loss. More research is needed before firm conclusions can be drawn about the effects of ghrelin. But, if we could create our bodies for one day, perhaps we’d simplify the actions of ghrelin and leptin and overcome the appetite stimulating effects of the “hunger hormone.”
Beyond this wish, the reality is that the human body has a complex system of hormones that interact in countless ways. Therefore, we are not likely to find a simple one-to-one relationship between these hormones and weight, or that ghrelin and leptin are likely part of a chain of physiological processes; too bad. We could use a villain when considering the challenges of obesity.
Do you eat to live or live to eat? We have a complicated relationship with food, influenced by cost, availability and even peer pressure. But something we all share is appetite – our desire to eat.Hormone and Appetite During Puberty Paper
While hunger – our body’s way of making us desire food when it needs feeding – is a part of appetite, it is not the only factor. After all, we often eat when we’re not hungry, or may skip a meal despite pangs of hunger. Recent research has highlighted that the abundance of food cues – smells, sounds, advertising – in our environment is one of the main causes of over consumption.
Our appetite is also not fixed, it changes across our lifespan as we age. As Shakespeare might have put it, there are seven ages of appetite, and a better understanding of these phases could help us to develop new ways of tackling under-eating and over consumption, along with the health effects, such as obesity, that follow.
The first decade, 0-10
In early childhood, the body goes through rapid growth and dietary behaviour built up in early life can extend into adulthood, leading a fat child to become a fat adult.
Fussiness or fear of particular foods can also contribute to meal time struggles for parents of young children, but a strategy of repeated tasting and learning in a positive environment can help children learn about unfamiliar but important foods, such as vegetables.Hormone and Appetite During Puberty Paper
Fussiness over certain foods can lead to eating issues in later life (Credit: Getty Images)
Children should also experience some control, particularly in relation to portion size. Being forced to “clear the plate” by parents can lead youngsters to lose their ability to follow their own appetite and hunger cues, promoting overeating in later years. There are growing calls for governments to protect young children from targeted junk food advertising – not just on television but in apps, social media and video blogs – since food advertising increases food consumption, which can contribute to children becoming overweight.
The second decade, 10-20
In the teenage years, a growth in appetite and stature driven by hormones, signals the arrival of puberty. How a teenager approaches food during this critical period will shape their lifestyle choices in later years.
This means the dietary decisions that adolescents make are intrinsically linked to the health of the future generations that they will later become parents to. Unfortunately, without guidance, teenagers may adopt eating behaviors and food preferences associated with unhealthy consequences.
Young women in general are more likely to suffer from nutritional deficiencies than young men because of their reproductive biology. Teenage girls who become pregnant are also at greater risk since their bodies are supporting their own growth in competition with that of the growing fetus.Hormone and Appetite During Puberty Paper
The third decade, 20-30
As young adults, lifestyle changes such as going to college, getting married or living with a partner, and parenthood can promote weight gain.
Once accumulated, body fat is often difficult to lose. The body sends strong appetite signals to eat when we consume less than our energy needs, but the signals to prevent overeating are weaker, which can lead to a circle of over-consumption. There are many physiological and psychological factors that make eating less difficult to maintain over time.
The stress we undergo in our 20s and 30s can cause us to put on weight (Credit: Getty Images)
An area of new research is to develop satiety, the sense of having eaten enough. This is helpful when trying to lose weight, since feeling hungry is one of the main barriers to eating less than your body says you need.
Different foods send different signals to the brain. It’s easy to eat a tub of ice cream, for example, because fat doesn’t trigger signals in the brain for us to stop eating. On the other hand, foods high in protein, water or fiber content make us feel fuller for longer. Working with the food industry provides an opportunity to shape the future of meals and snacks in beneficial ways.Hormone and Appetite During Puberty Paper
The fourth decade, 30-40
Adult working life brings other challenges beyond a rumbling stomach, but also the effects of stress, which has been shown to prompt changes in appetite and eating habits in 80% of the population, equally divided between those that gorge and those that lose their appetite.
These different coping strategies are intriguing: the phenomena of “food addiction” – an irresistible urge to consume specific, often high-calorie foods – is not well understood. Many researchers even question its existence.
Other personality traits, such as perfectionism and conscientiousness, may also play a role in mediating stress and eating behaviour.
Structuring the work environment to reduce problematic eating patterns such as snacking or vending machines is a challenge. Employers should strive to subsidies and promote healthier eating for a productive and healthy workforce, along with ways of managing stress and stressful situations.Hormone and Appetite During Puberty Paper
The fifth decade, 40-50
The word diet comes from the Greek word diaita meaning “way of life, mode of living”, but we are creatures of habit, often unwilling to change our preferences even when we know it is good for us. We want to eat what we want without changing our lifestyle, and still have a healthy body and mind.
In middle age, stress can lead us to become addicted to high-calories foods (Credit: Getty Images)
There is much evidence to show that diet is a major contributing factor to ill-health. The World Health Organization highlights smoking, unhealthy diet, physical inactivity and problem drinking as the main lifestyle impacts on health and mortality.
It is between the ages of 40-50 that adults should change their behaviour as their health dictates, but symptoms of illness are often invisible – for example high blood pressure or cholesterol – and so many fail to act.Hormone and Appetite During Puberty Paper
The sixth decade, 50-60
After the age of 50, we begin to suffer a gradual loss of muscle mass, at between 0.5-1% per year. This is called sarcopenia, and lessened physical activity, consuming too little protein, and menopause in women will accelerate the decline in muscle mass.
A healthy, varied diet and physical activity are important to reduce the effects of ageing, and an ageing population’s need for palatable, cost-effective, higher-protein foods is not being met.
Protein‐rich snack foods might represent an ideal opportunity to increase total protein intake in older adults, but there are currently few products designed to meet the requirements and preferences of older adults. (Read more about how much protein we need)
The seventh decade, 60-70, and beyond
A major challenge today in the face of increasing life expectancy is to maintain quality of life, or else we will become a society of very old and infirm or disabled people.
In later life, adequate nutrition is even more important to maintain health (Credit: Getty Images)
Adequate nutrition is important, as old age brings poor appetite and lack of hunger, which leads to unintentional weight loss and greater frailty. Reduced appetite can also result from illness, for example the effects of Alzheimer’s disease.
Food is a social experience, but the loss of a partner or family and eating alone affect the sense of pleasure taken from eating. Other affects of old age, such as swallowing problems, dental issues, reduced taste and smell also interfere with the desire to eat and our rewards from doing so.
We should remember that throughout life our food is not just fuel, but a social and cultural experience to be enjoyed. We are all experts in food – we eat it every day.
So we should strive to treat every opportunity to eat as an opportunity to enjoy our food and to enjoy the positive effects eating the right foods can have on our health.
Hunger hormones and appetite
Hormones control many processes in our body, including appetite.
Leptin, “the hormone of energy expenditure”, is found in the fat tissue and is responsible for hunger reduction. It signals the brain that the body has enough nutrients and fats.Hormone and Appetite During Puberty Paper
The more fat tissue you have, the more leptin is released. Since it is produced while you are sleeping, the lack of sleep lowers the level of leptin.
On the other hand, ghrelin, “the hunger hormone”, makes your appetite run wild. It is released in the stomach and gives the brain a signal: “Famine!”
The level of ghrelin determines how soon you will want to eat again after having a meal.
Studies have shown that a diet high in complex carbohydrates and protein, as well as a sufficient amount of sleep at night, produces adequate levels and balance of these hormones and avoids uncontrolled hunger pangs.
Why might you not feel full while eating?
It is natural for the body to feel hunger a few hours after eating. This way, it signals the need to replenish its energy reserves. However, if you constantly want to eat, you should consult a specialist.
A spike in appetite may be caused by:
lack of sleep
consuming too much food rich in fats and simple carbohydrates (fast food, candy), as well as sweet carbonated drinks
medications (antihistamines, antidepressants, steroids, some drugs for diabetes, anti psychotics)
low blood sugar in the case of hepatitis, renal, or adrenal failure Hormone and Appetite During Puberty Paper
diabetes (While blood sugar level is increased, its delivery to cells is inhibited due to lack of insulin, and the cells don’t get enough nutrients.)
How to avoid overeating
If you want to keep fit, the most important thing is to maintain an energy balance, consuming as many calories as you burn.
If you want to deal with increased appetite, adhering to strict diets may be difficult and may lead to eating disorders. Extreme weight loss measures are dangerous.
Follow these recommendations to lose extra pounds:
eat 3–4 times a day
follow a balanced diet (Compare the diet consisting of 1–2 products (the mono diet), and the diet that includes fish, vegetables, and grains. At the same caloric value they can have different effects on the body.)
This will give you a feeling of lightness and eliminate constant hunger.
Even though it has been proven that the quality of food and the amount of nutrients is ultimately more important than the frequency of meals and the volume of portions, you can keep a healthy metabolism and avoid unplanned snacking if you eat every 3-4 hours, focusing on the feeling of hunger.Hormone and Appetite During Puberty Paper
Constant hunger may indicate that the body lacks certain nutrients and vitamins.
You can fix this by including complex carbohydrates, proteins, vegetables, and fruit in your diet.
How to cope with overeating?
The habit of overeating is often caused by chronic stress, lack of sleep, and changes in hormonal levels (for example, before menstruation).
Even if there are healthy foods on your plate, large quantities will give you a surplus of calories at the end of the day, which can cause weight gain.
These simple rules will help you keep your food habits under control:
Do not let strong hunger occur. Determine the optimal number of meals for you. The more often you eat, the smaller the portions should be. The optimal number of meals is three or four.
Drink a glass of water 20 minutes before eating, and every time your stomach growls at an inopportune time. Often, thirst causes false hunger.
Be sure to include in your diet a sufficient amount of protein and fiber.
Chew your food slowly. Do not get distracted by a TV, a phone, or a book. It can make you eat much more than you planned.
How can exercise help you cope with increased appetite?
Increased appetite and overeating is a normal response of your body to try to raise serotonin and lower cortisol levels.
Scientists recommend substituting an unscheduled meal with physical activity, such as swimming or running.
For optimal benefits, experts recommend 30 minutes of exercise, 4 to 6 times per week. However, even a quick 10-minute walk can deter cravings.Hormone and Appetite During Puberty Paper
Snacks to lose weight are real!
Planning healthy snacks will help you avoid binge eating. Snacking prevents strong hunger between meals and helps to maintain your blood sugar levels.
Sharp sugar surges can trigger type 2 diabetes, cardiovascular diseases, hypertension, and obesity. It makes you eat more than your body really needs.
Do not snack right before the main meal. Make sure your increased appetite is true. Don’t eat because you are bored.
Studies show that having 3–4 meals a day allows you to control your weight easier.
Properly selected snacks will help you balance your diet better. For these purposes choose a vegetable salad, not very sweet fruit, high-quality plain yogurts, and nuts.
Keeping your appetite tamed, especially with some of the risk factors mentioned above, is not easy. But if it becomes a matter of health, you have to do everything you can to stop overeating. And if you find it too difficult or face the complications you cannot fight, consult a doctor.
Our bodies have hormones that regulate every aspect of metabolism, and that includes appetite and weight regulation. Several hormones have been discovered that affect appetite and the development or prevention of obesity. There are four major such hormones: ghrelin, leptin, insulin, and peptide YY (PYY). This article focuses on leptin.Hormone and Appetite During Puberty Paper
What Is Leptin?
Simply stated, leptin is a hormone that suppresses appetite. It has been termed a “satiety factor” for this reason. Leptin is produced by adipose (fat) cells. The level of its production is thus in proportion to body fat. When body fat levels increase, so do levels of leptin, which then serves to suppress appetite and increase basal metabolic rate. When body fat levels fall, so do levels of leptin, and appetite suppression is removed, signaling to the body that it is time to eat again. Originally, this served the purpose of preventing starvation.
Leptin is sometimes thought of as ghrelin’s counterpart because ghrelin (another appetite-regulating hormone, produced by the stomach and duodenum) stimulates appetite as its levels rise. Because leptin can reduce food intake by suppressing appetite, it can induce weight loss; counter to that, because ghrelin can increase food intake by stimulating appetite, it can cause weight gain and obesity.
In 1994, the gene that produces leptin, known as the human obese (OB) gene, was discovered by Zhang and colleagues in mice. Leptin has been reported to have multiple biological functions, including immune and inflammatory responses, a role in the initiation of human puberty, a role in bone formation, and a role in wound healing, among others and in addition to its role in weight regulation.
What Affects Leptin Levels?
Researchers have discovered a number of behaviors and factors that can either increase or reduce leptin levels in the body. The size and frequency of meals seem to play a role in the release of leptin from adipose tissue. In addition, the composition of a meal is important. In some studies, for instance, low-fat meals seemed to result in higher levels of circulating leptin than high-fat meals. There is also evidence that obese patients have become leptin-resistant, or resistant to the effects of leptin, and thus the normal biological regulatory pathway that tells the body when it is time to stop eating has been disrupted.
Too little sleep may also affect levels of leptin, resulting in lower levels and greater appetite (working in concert with ghrelin, as noted above). Getting the recommended seven to nine hours of uninterrupted sleep every night seems to help keep leptin levels where they should be in response to meals.
As might be imagined, due to its ability to induce weight loss, studies looking at different ways to utilize leptin and its functions for pharmacologic therapy have been ongoing for some time and are part of the continuing search for successful anti-obesity therapies.
Ghrelin is the only known peripherally produced and centrally active orexigenic hormone that is considered to be an important gut-brain signal for appetite control and energy balance. Its first recognised action was stimulation of growth hormone (GH) release from the pituitary gland but it also stimulates prolactin and ACTH and may inhibit LH/FSH. In addition to its orexigenic and pituitary activity, ghrelin acts on various systems, such as the gastrointestinal, cardiovascular, pulmonary, reproductive, and central nervous systems. The muscle effects of ghrelin involve stimulatory action on the cardiac muscle, vascular smooth muscle, ocular smooth muscle, gastrointestinal smooth muscle, and skeletal muscle and via the GH effect also on bone.1,2 Ghrelin and its receptors are found in the reproductive organs and in the placenta, and during pregnancy and lactation ghrelin regulates maternal energy intake.3 Furthermore, ghrelin could also act as a regulator of the gonadotropic axis.4 It has recently been shown that ghrelin plays a role in the regulation of sodium reabsorption in the cortical collecting ducts of kidneys.5 Ghrelin levels have been found to be altered in various conditions, examples of which are summarised in Table 1. In this paper we focus on the role of ghrelin in obesity, Prader-Willi syndrome, anorexia and other eating disorders, and cachexia, as well as on the implications of ghrelin as a pharmacological target in relation to these disorders.Hormone and Appetite During Puberty Paper
Structure, receptor, and signalling pathway
Ghrelin is a 28-amino-acid peptide that is mainly produced by the neuroendocrine cells (named “X/A like” in rat and “P/D1” in humans) in the oxyntic mucosa of the gastric fundus.19 Ghrelin is also produced in areas of the gastrointestinal tract and other peripheral organs but in lesser amounts. The 117-amino-acid preproghrelin protein is encoded by the human ghrelin gene on chromosome 3p25-26. Ghrelin is first cleaved from the preproghrelin polypeptide at the N-terminal by the prohormone convertase 1/3. An octanoic acid then esterifies a hydroxyl group of the third N-terminal amino-acid serine residue of the proghrelin peptide to form acyl ghrelin. Yang et al (2008) demonstrated that the enzyme that attaches octanoate to serine-3 of ghrelin is GOAT (Ghrelin O-Acetyltransferase); this leads to the acylation of ghrelin which is required in order that ghrelin can bind to its receptor.20 However, not all ghrelin is active acylated ghrelin; in fact, only a minority of the circulating ghrelin is acylated. Initially, it was thought that only acyl ghrelin activates the classical growth hormone secretagogue receptor (GHSR) expressing cells, whereas the nonmodified des-n-octanyl form of ghrelin (desacyl ghrelin) does not.21 Meanwhile, although desacyl ghrelin was originally considered an inactive by-product of ghrelin secretion or degradation, recent evidence suggests that desacyl ghrelin acts in peripheral tissues and in the brain to regulate biological actions. A study by Heppner et al (2013) has shown that both acyl ghrelin and desacyl ghrelin significantly increased IP3 formation in HEK-293 cells transfected with human GHSR.22 Intracerebroventricular (icv) infusion of desacyl ghrelin in mice increased fat mass at the highest dose tested, as well as glucose-stimulated insulin secretion. In contrast, icv desacyl ghrelin failed to regulate fat mass and induce hyperinsulinaemia in GHSR deficient (Ghsr-/-) mice. Desacyl ghrelin also failed to regulate these parameters in control mice when it was administered subcutaneously. Based on these findings, the authors suggested that desacyl ghrelin is an agonist of GHSR and regulates body adiposity and peripheral glucose metabolism through a CNS GHSR-dependent mechanism.22
GHSR has two variants: GHSR1a and GHSR1b. GHSR1a is able to bind acylated ghrelin, whereas GHSR1b is physiologically inactive, although one study suggested a dominant-negative, antagonistic role.23 The results of this study showed that when the expression of GHSR1b exceeded that of GHSR1a, there was a decrease in the cell surface expression of GHSR1a with a consequent decrease in constitutive activation of phosphatidylinositol-specific phospholipase C. GHSR1a is a highly conserved G-protein coupled receptor and both GHSR1a and 1b have a wide expression in different tissues, with a role in various systems such as cardiovascular, immune, gastrointestinal, reproductive, and endocrine. GHSR1a is predominantly expressed in the pituitary and at much lower levels in the thyroid gland, pancreas, spleen, myocardium, and adrenal gland.24 Interestingly, the locus of the GHSR gene has been implicated in the determination of height.25
Feedback systems and appetite regulation
The first recognised effect of ghrelin was the induction of GH release from the somatotroph cells of the anterior pituitary. Moreover, by acting centrally or via vagal afferents, ghrelin can activate hypothalamic arcuate neurons that secrete the orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide, and inhibit the anorexigenic neurons secreting α-melanocyte-stimulating hormone (α-MSH). Arcuate neurons project to paraventricular, lateral hypothalamic, and other nuclei, as well as orexin in the lateral hypothalamus, which could contribute to the orexigenic effects of ghrelin.26 Ghrelin is the first known peripheral hormone that can induce orexigenic effects through acting on hypothalamic pathways; moreover, it is active even with peripheral administration, in contrast to most orexigenic peptides which are only active when injected into the brain. Ghrelin is considered to be the peripheral counterpart of insulin and leptin, as it exerts opposite effects compared to these hormones (Figure 1). A study on healthy volunteers demonstrated that ghrelin reduces glucose-stimulated insulin secretion, leading to deterioration of glucose tolerance.28 Moreover, the results of the CODING study demonstrated that a high circulating ghrelin level is associated with lower insulin resistance in the general population.27 In addition, Tong et al showed that physiologic concentrations of exogenously infused ghrelin reduce insulin secretion without affecting insulin sensitivity in healthy humans, indicating that ghrelin antagonism could improve β-cell function.28
Figure 1. Simplified scheme showing that ghrelin stimulates the NPY/AGRP orexigenic pathway and inhibits the POMC-related anorectic pathway, resulting in increased food intake.
Tschop et al demonstrated that peripheral daily administration of ghrelin caused weight gain by reducing fat utilisation in mice and rats, this implying that ghrelin can induce an increase in adipose tissue and body weight.29 Consistent with these results are the findings that ghrelin increases the mRNA expression of fat storage enzymes whilst decreasing the expression of the rate-limiting step in fat oxidation, carnitine palmitoyl transferase-1alpha.30 These results may suggest that ghrelin induces a metabolic switch from the utilisation of fat to carbohydrates, whereas energy expenditure does not appear to be affected.
It has been proposed that ghrelin acts as an initiator signal for food consumption in humans: repeated plasma samples throughout a 24-h period demonstrated a clear preprandial rise and postprandial fall in plasma ghrelin levels, indicating that ghrelin can play a physiological role in meal inititation.31Hormone and Appetite During Puberty Paper
More recently an important interplay has been demonstrated between glucagon and ghrelin. The mechanisms by which glucagon induces satiety are not completely understood and it has been suggested that glucagon-induced reduction in total ghrelin exerted at the hypothalamo-pituitary level might be responsible for this effect.32
The role of ghrelin in reward-based eating
GHSR1a is expressed in various nodes of the mesolimbic system, which include the ventral tegmental area (VTA) and the nucleus accumbens (NAc). More than 50% of dopaminergic VTA neurons co-express GHSR1a and are also present in GABAergic VTA neuronal subpopulations, which regulate the activity of the dopaminergic neurons.33 It has been proposed that ghrelin can increase the dopaminergic transmission from VTA to the NAc, leading to augmentation of afferent reward signals. A recent study using a rat model demonstrated that VTA injections of ghrelin produced a significant increase in food motivation/reward behaviour, as measured by sucrose-induced progressive ratio operant conditioning, and chow intake. Moreover, pretreatment with either a D1-like or D2 receptor antagonist into the NAc completely blocked the reward effect of ghrelin, leaving chow intake intact.34 These results imply that the VTA to NAc dopaminergic projections, along with D1-like and D2 receptors in the NAc, are essential elements of the ghrelin responsive circuits controlling food reward behaviour.
Homeostatic feeding is thought to be under the control of circulating hormones acting primarily on the hypothalamus. The mechanisms by which ghrelin promotes food intake are not only homeostatic but also include enhancement of the rewarding effects of certain foods so that extra effort is made to obtain the pleasurable food, “hedonic feeding”.35 Hedonic feeding occurs in the absence of nutritional and caloric deficiency and can be described as “non-homeostatic”. Functional magnetic resonance imaging (fMRI) following ghrelin administration demonstrated an increased neural response to food pictures in regions of the brain, including the amygdala, orbitofrontal cortex, anterior insula, and striatum, implicated in encoding the incentive value of food cues.36 The effects of ghrelin on the amygdala and orbitofrontal cortex response were correlated with self-rated hunger ratings.36 The results of this study suggest that metabolic signals such as ghrelin may favour food consumption by enhancing the hedonic and incentive responses to food-related cues.
Several studies have investigated the role of ghrelin in defining food preference. Ghrelin shifts food preference to diets rich in fat29 or sweet food, regardless of whether the food has caloric content. Ghrelin increased the preference for 0.3% saccharin solution in wild type mice, while it did not have an effect in GHSR1 deficient mice, indicating that the ghrelin receptor pathway is necessary to mediate these phenomena.37 In addition to enhancing preference for fatty and sweet foods, ghrelin also mediates more complex reward-based eating behaviours. Some studies have used the conditioned place preference test, which involves comparing the amount of time animals spend in an environment with which they have been conditioned to find a pleasurable diet to the time spent in a distinct environment associated with regular chow or no food. Another method that has been used is operant conditioning, for example operant lever pressing for high-rewarding foods. Studies have demonstrated that by using both the conditioned place preference test and operant conditioning, ghrelin enhanced the rewarding value of a high-fat diet when administered to ad lib-fed mice; by contrast, wild-type mice treated with ghrelin receptor antagonist and ghrelin receptor-null mice both failed to show conditioned place preference test to high-fat diet normally observed under calorie restriction.38,39 Furthermore, use of GHSR1 antagonists reduced operant responding for sucrose solution, as it was found that the intake and self-administration of sucrose in rats was reduced, as was also saccharin intake in mice.40
Various studies have demonstrated that plasma ghrelin levels in obese individuals are low and inversely proportional to body mass index.41 Subjects with insulin resistance and high insulin levels also experience chronically low ghrelin levels. For example, a study analysing the fasting plasma ghrelin concentrations of 1,040 subjects demonstrated that ghrelin concentrations were negatively associated with fasting insulin and insulin resistance.15 Ghrelin concentrations are also different in obese and normal-weight pre-pubertal children: in response to intake of a standardised breakfast, obese children showed an early recovery of postprandial ghrelin levels to baseline levels at 3 hours, while ghrelin levels remained suppressed after 3 hours in normal-weight children.42 In addition to ghrelin levels being low in obese individuals, it has also been suggested that diet-induced obesity causes ghrelin resistance in NPY/AgRP neurons. Diet-induced obesity suppresses the neuroendocrine ghrelin system by decreasing acylated and total plasma ghrelin, decreasing ghrelin and GOAT mRNA in the stomach, decreasing expression of hypothalamic GHSR, and decreasing expression of Npy and Agrp mRNA.43Hormone and Appetite During Puberty Paper
It has been proposed that genetic polymorphisms of the ghrelin gene may play a role in the relationship of ghrelin and obesity. The Leu72Met change in the preprogherin protein and the Arg51Gln variant at the end of mature ghrelin product (therefore possibly interfering with protein cleavage) has been studied in several cohorts,44-46 but reproducible robust correlations were not found. The GHSR gene has also been studied in obese and diabetic populations47,48 with, however, no consistent results. Interestingly, the GHSR gene has been identified as factor in determining height.25 Rare loss-of-function mutations have been identified in short children. Moreover, Pugliese-Pires et al reported inactivating mutations in the GHSR1 gene in patients with constitutional delay of growth and puberty.49
The role of ghrelin in genetic obesity is an interesting question. Ablation of ghrelin in leptin-deficient ob/ob mice increases insulin secretion and improves hyperglycaemia. Surprisingly however, GHSR ablation worsened the hyperglycaemia, decreased insulin, and impaired glucose tolerance.50 Five human homozygous leptin mutation patients and eight heterozygous carriers were studied for postprandial hormone changes. Plasma ghrelin levels in homozygotes remained remarkably unchanged following food consumption in contrast to a significant decline in heterozygous and normal subjects.51 The effect of MC4R single nucleotide polymorphisms (SNPs) was examined in a large family study; to qualify for the study, families were required to have at least one overweight child between the ages of 4 and 19 years old. The results showed that genetic variation in MC4R plays a functional role in the regulation of physical activity, energy expenditure, and fasting serum ghrelin in Hispanic children; moreover, one of the SNPs (rs34114122) was selected as having likely functional effects on ghrelin, as Bayesian quantitative trait nucleotide analysis strongly supported a functional effect for rs34114122 on fasting serum ghrelin with a strong posterior probability (0.81).52 A link has recently been identified between the obesity-related FTO gene and ghrelin.53 The results demonstrated that the subjects homozygous for the FTO obesity-risk variant had dysregulated circulating levels of acyl ghrelin and attenuated postprandial appetite reduction; moreover, postprandial functional MRI showed that the same subjects had increased neuronal activity in brain regions controlling appetite, reward, and motivation after a test meal. The authors suggested that the FTO genotype can alter the way the brain responds to circulating ghrelin. They moreover proposed a direct link between FTO risk alleles and ghrelin action, as it was found that FTO overexpression in cell-based assays increased ghrelin mRNA expression and total levels of active ghrelin compared with controls, whereas methylation of ghrelin mRNA was reduced. A prospective study used cross-sectional data from 985 elderly patients and demonstrated a positive relationship between the number of FTO C risk alleles (rs17817449) and plasma ghrelin levels; conversely, serum levels of the satiety-enhancing hormone leptin were inversely linked to the number of FTO C risk alleles.54 These associations imply that FTO may facilitate weight gain in humans by shifting the endocrine balance from leptin towards ghrelin.
The Prader-Willi syndrome (PWS) is the most common cause of syndromic obesity, and results from paternally inherited genes in the q11-13 region of chromosome 15.55 The SNORD116 locus lies in the 15q11-13 region of paternally expressed genes implicated in PWS and it has been proposed that lack of the paternal SNORD116 gene cluster has a determinant role in the pathogenesis of PWS.56 It is characterised by initial poor feeding followed by hyperphagia from the age of 12 months leading to morbid obesity if uncontrolled. Despite their high BMI, several studies found high ghrelin levels in PWS adults and even more in children compared to normal subjects and BMI matched simple obese patients.57-59 These studies might indicate that the hyperphagia observed in PWS could be secondary to elevated ghrelin levels. However, we need to keep in mind that PWS patients are not insulin resistant, rather they have increased insulin sensitivity. A more recent cross-sectional study measuring fasting plasma ghrelin levels in very young children with PWS (n=42) and controls (n=9) aged 7 months to 5 years found no hyperghrelinaemia in young children with PWS, and ghrelin changes were not associated with the timing of the transition to the characteristic hyperphagic phase. The authors suggested that abnormal and/or delayed development or sensitivity of the effector pathways of ghrelin (for example, parasympathetic and central nervous system) may interact with later hyperghrelinaemia to contribute to hyperphagia in PWS.60
In regard to the studies demonstrating elevated ghrelin levels in PWS, several hypotheses have been put forward to account for these observations.61 An increased number of ghrelin-producing cells in the gastric body and fundus of PWS patients could lead to elevated ghrelin levels.62 Imprinting of paternal genes in region q11–13 on chromosome 15 may induce the production of excessive amounts of transcription factors that increase ghrelin expression. There could also be loss of a transcription inhibitory factor that normally suppresses ghrelin expression.63 Reduced visceral adiposity and relative hypoinsulinaemia could partially explain hyperghrelinaemia in PWS.64 Abnormal parasympahetic vagal innervation of the stomach and abnormal sympathetic tone in PWS patients might also explain the high ghrelin levels.65 Moreover, a study has shown that ghrelin dysregulation in PWS occurred very early and preceded the onset of obesity, indicating that in the first years of life, hyperghrelinaemia in PWS may be a response to failure to thrive or food restriction.66 The lack of ghrelin suppression after meals in PWS adults59 but not in PWS children67 may imply that the progressive deterioration of PWS could result in a multistep developmentally driven process in ghrelin dysregulation. Also, in adults with PWS, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels. A study by Purtell et al points to the fact that compared to adiposity-matched control subjects, hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response and that elevated ghrelin levels in PWS are consistent with increased hunger and are unrelated to insulin levels.68
Anorexia nervosa (AN) is the most common cause of weight loss in young women and of admission to child and adolescent services.69 Moreover, anorexia nervosa has the highest mortality of any psychiatric disorder.70 It is characterised by refusal to maintain body weight at or above minimally normal weight, intense fear of gaining weight or becoming fat, and disturbance in the way body weight or shape is experienced. The aetiology of anorexia nervosa is not currently well understood. Recently, some studies have focused on the relationship between hunger regulation and gut-brain peptides; in particular, numerous data show that alterations of central and/or peripheral peptidergic signalling are related to disturbed regulation of feeding and body weight, peptidergic signalling including anorexigenic corticotropic-releasing factor, melanocortin, NPY, and ghrelin.
In terms of ghrelin levels, several studies have reported that individuals with anorexia nervosa have higher levels of fasting plasma ghrelin than normal weight healthy controls. For example, Monteleone et al compared 20 female anorexia nervosa patients with 20 healthy women; it was found that AN patients displayed significantly increased circulating levels of ghrelin compared to healthy patients.71 In another study,Hormone and Appetite During Puberty Paper Nedvikova et al investigated responses of plasma ghrelin to food intake, meal volume, and meal nutritional value in healthy volunteers and women with anorexia nervosa; it was found that fasting plasma ghrelin was significantly higher in AN patients than in controls and correlated negatively with percentage of body fat in both groups. Ghrelin levels markedly fell after consumption of either a standardised meal or fibre in controls, but not in anorexic women.72 These results indicate that the acute plasma ghrelin response to food intake is impaired in AN patients. The authors suggested that this response could be part of a chronic adaptation to prolonged food restriction which attempts to restore normal feeding conduct by maintaining the drive to eat. Another study by Tolle et al involved assessing ghrelin plasma levels in anorexia nervosa patients before and after re-nutrition and in constitutionally thin subjects with BMIs equivalent to those of AN women but with no abnormal feeding behaviour.73 It was found that morning fasting plasma ghrelin levels were doubled compared with levels in controls and constitutionally thin subjects and that 4- and 24-hour ghrelin levels were increased compared to controls. These results indicate that ghrelin levels are not only dependent on body fat mass but are also affected by nutritional status.
The reduced food intake that characterises anorexia nervosa, despite the chronically increased ghrelin levels, may suggest that this condition represents a state of “ghrelin insensitivity or resistance”. This theory is supported by results that showed that anorexia nervosa patients did not respond to ghrelin administration by increasing appetite and food intake as did healthy controls.74 Ogiso et al comment that although many studies have investigated the association between anorexia nervosa and ghrelin, most studies measured total ghrelin and did not distinguish between acyl ghrelin and desacyl ghrelin.26 This could play a role as to how results are interpreted, as certain studies have found that desacyl ghrelin has opposite effects to acyl ghrelin. For example, Asakawa et al demonstrated that desacyl ghrelin induces a negative energy balance by decreasing food intake and delaying gastric emptying in mice.75 The results of these studies contradict the previously mentioned findings of Heppner et al according to which desacyl ghrelin is an agonist of GHSR leading to increased fat mass and increased glucose-stimulated insulin secretion.22 In a study by Koyama et al, the changes in ghrelin levels (both acyl and desacyl) during early treatment of anorexia nervosa were measured.76 It was found that desacyl ghrelin in anorexia nervosa patients was higher than in control subjects before the therapy, but it decreased with treatment and was significantly lower than in control subjects after 8 weeks of treatment; moreover, the ratio of the acyl ghrelin to total ghrelin increased with 8 weeks’ treatment. These results may suggest that a successful refeeding outcome could involve increasing acyl ghrelin and decreasing desacyl ghrelin. In conclusion, future studies investigating ghrelin levels in anorexia nervosa could measure both acyl and desacyl ghrelin in order to obtain a clearer picture of the role of ghrelin in anorexia nervosa.
It currently remains unknown why ghrelin levels are higher in anorexia nervosa patients than in healthy controls and why people with anorexia nervosa do not respond appropriately to ghrelin. Terashi et al proposed that changes of ghrelin reactive autoantibodies could explain elevated plasma ghrelin in AN.77 Autoantibodies to ghrelin occur naturally, and it is thought that physiologic ghrelin autoantibodies help regulate the ghrelin plasma levels.41 The autoantibodies could alter the feeding-regulatory circuitry and behaviour by changing the signalling of the molecule, ranging from transport to neutralisation.26 In their study, Terashi et al found that patients with anorexia nervosa had significantly lower plasma levels of acyl ghrelin IgG, IgM, and IgA autoantibodies; the levels remained low even after one month of refeeding.77 The authors proposed that the decrease of bioavailable ghrelin autoantibodies may underlie a long-term elevation of plasma ghrelin levels and the resulting phenomenon of ghrelin resistance in malnourished patients with anorexia nervosa.
Differences in ghrelin levels have also been noted in regard to the type of anorexia nervosa. Whereas studies have recorded increased ghrelin levels in restrictive anorexia nervosa, others have reported unchanged ghrelin levels in binge-purge anorexia nervosa.78,79
Further research is needed to fully elucidate the ghrelin effects and the ghrelin level fluctuations in anorexia nervosa. In addition, further investigations are required to determine whether any genes for ghrelin can predispose individuals to anorexia nervosa. It has been hypothesised by Dardennes et al (2007) that ghrelin and AgRP polymorphisms confer susceptibility to anorexia nervosa; the results of their study demonstrated a transmission disequilibrium for the Leu72Met variant of the preproghrelin gene and an excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with anorexia nervosa (bingeing-purging subtype).80 Moreover, Muller et al observed an association of a GOAT gene variant with AN in a study involving 543 German patients with AN and 612 German normal and underweight healthy controls.81 A genetic variation of the ghrelin activator gene MBOAT4 was implicated as a causal factor in anorexia nervosa,81 and the 3056T>C SNP of the ghrelin gene was suggested in another as being related to recovery from restrictive anorexia nervosa.82 However, Kindler et al found no increased occurrence of 3 ghrelin gene polymorphisms in patients with eating disorders compared with in healthy controls.83
Bulimia nervosa (BN) is characterised by eating in a discrete period of time an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances. In addition, a sense of lack of control over eating during the episode and recurrent inappropriate compensatory behaviour to prevent weight gain characterise the syndrome.84
Ghrelin levels in bulimia nervosa are variable according to the clinical study and various results have been obtained. BMI matched bulimia nervosa patients had significantly higher fasting plasma ghrelin levels compared to healthy volunteers.85,86 However, other studies found no significant differences.71,87 It has been suggested that the differences in the results of these studies could be attributed to the different methods being used, for example radioimmunoassay vs. ELISA, or measuring fasting vs non-fasting ghrelin levels.88 Reduced ghrelin suppression after eating was found in some studies and it has been theorised that this blunted postprandial decrease in ghrelin levels could indicate a reduced satiety response, which could in turn explain the binges.86,89
When comparing bulimia nervosa with anorexia nervosa patients, fasting plasma ghrelin levels were found to be significantly lower in women with binge-eating and purging behaviour compared to restricting type anorexia nervosa patients.90
It is possible that ghrelin gene polymorphisms could be associated with vulnerability for bulimia nervosa. For example, it has been found that the C allele at the 3056T>C SNP (CC and TC genotypes) in intron 3 and the Met allele at the Leu72Met SNP of the ghrelin gene were significantly more frequent in purging-type BN.82 Moreover, a GHSR gene variant that was associated with BN in Japanese patients.91
Cachexia is defined as a complex metabolic syndrome associated with underlying illness and characterised by loss of muscle with or without loss of fat mass.92 Cachexia is distinct from starvation, age-related loss of muscle mass, primary depression, malabsorption, and hyperthyroidism and is associated with increased morbidity. It can occur in patients with advanced cancer and/or chronic progressive diseases.93 Malnutrition has been observed in a variety of patients with chronic diseases, including congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), renal failure, and cancer.94 The inverse relationship between plasma ghrelin and BMI observed in healthy individuals also applies to cachectic patients, for example in underweight patients with chronic obstructive pulmonary disease,95 but there were no significant differences in ghrelin levels between normal subjects and cachectic (CHF, COPD, cancer) patients after matching for BMI.95,96 Some studies, however, have demonstrated elevated levels in cachectic patients with a variety of cancers.97 These elevated ghrelin levels could serve as a compensation for energy loss to maintain homeostasis and as a defence mechanism against starvation. Various factors could contribute to the increased ghrelin levels in certain cancers, and it has been reported that some cancers can express ghrelin.98 Elevated ghrelin levels have also been found in cachectic patients with chronic renal failure,99 but this might be due to increased desacyl ghrelin levels, whereas acyl ghrelin levels are not increased.100 It was suggested that the elevation in total ghrelin is secondary to the fact that desacyl ghrelin is cleared through the kidneys, leading to accumulation in renal insufficiency.41
APPLICATIONS IN CLINICAL PRACTICE
Ghrelin as a pharmacotherapy
In addition to lean and obese healthy volunteers, ghrelin administration studies have involved several patient populations including those with congestive heart failure, several types of cancer, diabetes mellitus, pulmonary disease, anorexia nervosa, end-stage renal disease, Cushing’s syndrome, gastroparesis, polycystic ovary syndrome, hyperthyroidism, hyperparathyroidism, depression, acromegaly, and GH deficiency.101 By reviewing these treatment studies Garin et al concluded that there is strong evidence that ghrelin is an effective appetite stimulant, resulting in increased energy intake but that there is less evidence that ghrelin can cause positive changes in body composition, and almost no evidence of an increase in muscle strength and performance.101Hormone and Appetite During Puberty Paper
Only a small number of studies have so far investigated the effects of ghrelin administration on patients with anorexia nervosa. The first study to investigate this, by Broglio et al, involved administration of ghrelin to nine women with anorexia nervosa (restricting type) and seven healthy women; the results indicated an impaired GH response to ghrelin in anorexia nervosa. Although food intake was not measured, hunger was mentioned as an adverse event.102 A more recent pilot study by Hotta et al investigated the effects of ghrelin on appetite, energy intake, and nutritional parameters in five patients with restricting-type AN who were fully motivated to gain body weight but could not increase their food intake because of malnutrition-induced gastrointestinal dysfunction. The daily energy intake of the five patients during the pre-treatment period ranged from 825 to 1426 kcal. During ghrelin infusion, four patients showed a statistically significant increase in daily energy intake. Mean increase in daily energy intake during ghrelin infusion was about 20% when compared with the pretreatment period. Analysis of nutrients revealed significant increases in daily intakes of carbohydrate in three patients, fat in one patient, and protein in all patients. The ghrelin administration improved epigastric discomfort and constipation and increased the hunger score.103 The results of these studies indicate that ghrelin could potentially be a new treatment for anorexia nervosa. However, a study by Miljic et al found that ghrelin administration did not significantly affect appetite in 25 young women with anorexia nervosa.74 It has been suggested that these results could be reflecting differences in population, treatment duration, and dose.89
Other studies investigated the effect of ghrelin administration on various cachectic conditions. Nagaya et al administered human synthetic ghrelin intravenously to 10 patients with congestive heart failure for three weeks. It was found that both food intake and body weight were increased; moreover, exercise capacity, muscle wasting, and left ventricular function were improved.104 An open label pilot study by Nagaya et al examined whether ghrelin could improve cachexia and functional capacity in seven cachectic patients with COPD. It was found that a three-week ghrelin treatment resulted in a significant increase in mean body weight, food intake, lean body mass, and peripheral and respiratory muscle strength; moreover, ghrelin attenuated the exaggerated sympathetic nerve activity.105 In a study by Wynne et al, nine peritoneal dialysis patients with mild to moderate malnutrition were administered ghrelin subcutaneously. The results demonstrated a significant increase in the group mean absolute energy intake, compared with placebo; moreover, ghrelin administration resulted in immediate doubling of energy intake when expressed as proportional energy increase for each individual.106 Other studies investigated the effects of administering ghrelin in the setting of cancer cachexia. Although the use of supra-physiological doses of ghrelin was generally required, the effects on appetite have been positive; this suggests that the effects of ghrelin on appetite-stimulating centres are not saturated in the setting of cancer cachexia. A randomised, placebo-controlled, cross-over clinical trial demonstrated appetite stimulation by ghrelin in seven cancer patients with cachexia; the results showed that administration of ghrelin significantly increased food intake and meal appreciation as compared to saline infusion.107 However, there are concerns regarding the use of ghrelin in cancer cachexia; for example, an important concern is that ghrelin may increase growth factors, such as GH and IGF-1, leading to stimulation of tumour growth.108 In addition, the short half-life of ghrelin and the route of delivery via injection are additional limitations of the use of ghrelin as a therapeutic agent.
Apart from exerting anti-cachectic effects by acting on the GHSR1a receptor, Porporato et al proposed that acyl and desacyl ghrelin could act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner.109 Their results demonstrated that both acyl and desacyl ghrelin inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kβ-, mTORC2-, and p38-mediated pathways in myotubes. Moreover, it was shown that acyl and desacyl ghrelin induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy in Ghsr-deficient mice.
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A recent double-blind placebo, controlled, cross-over study has indicated that desacyl ghrelin may improve glycaemic control in obese diabetic subjects by decreasing acylated ghrelin level.110 The study involved investigating the effects of continuous overnight infusion of desacyl ghrelin on acylated ghrelin levels and glucose and insulin responses to a standard breakfast meal in eight overweight patients with type 2 diabetes. It was found that, compared with placebo, overnight desacyl administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and in peak serum glucose levels; moreover, the degree of improvement in glycaemia was correlated with baseline plasma acylated ghrelin levels, which were decreased. The authors of the study suggested that desacyl ghrelin is a good candidate for the development of compounds in the treatment of metabolic disorders and conditions such as type 2 diabetes mellitus and PWS.
The administration of desacyl ghrelin may also have a clinical application. It has previously been demonstrated that desacyl ghrelin can counteract the effects of acyl ghrelin on insulin secretion and glucose metabolism: acyl ghrelin administration was followed by a decrease in insulin levels and an increase in plasma glucose levels; while desacyl ghrelin administration alone had no effects, desacyl ghrelin together with acyl ghrelin diminished the insulin and glucose response to acyl ghrelin.111 Moreover, it has been reported that i.v. desacyl ghrelin administration improves glucose metabolism and inhibits lipolysis in healthy volunteers.112 The results of these studies imply that desacyl ghrelin or desacyl ghrelin analogs might have a pharmacological application in the future treatment of metabolic disorders, diabetes, obesity, and PWS, as they could inhibit or suppress ghrelin.Hormone and Appetite During Puberty Paper
Ghrelin receptor agonists
Several ghrelin agonists are currently under development for various indications. For example, a recent phase 2a, randomised, double-blind 28-day study of the ghrelin receptor TZP-102 demonstrated a reduction of the symptoms of diabetic gastroparesis.113 Other targets of ghrelin receptor agonists include cancer cachexia, postoperative ileus, and opioid-induced bowel dysfunction.114 Palus et al used a rat model of congestive heart failure to investigate the effects of administering the ghrelin analogues BIM-28125 and BIM-28131; whereas placebo-treated rats gained no fat (but only lean mass), the active compounds induced both fat and lean mass gain.115 In a recent study, Lenk et al also used a rat model of congestive heart failure and showed that the same analogues significantly increased the expression of myostatin in the skeletal muscles of the rats.116 In a human study of healthy volunteers, the oral ghrelin agonist and GH secretagogue RC-1291 produced dose-related increases in body weight with no dose-limiting adverse effects; the authors suggested that RC-1291 could be an effective treatment for cancer-associated cachexia and anorexia.117
Ghrelin receptor antagonists
Various pharmacological tools are being investigated to counteract the effects of ghrelin (Figure 2). The ghrelin receptor antagonists are an example of these tools. A study by Beck et al involved administering the ghrelin receptor antagonist [D-Lys)]-GHRP-6 to fa/fa obese Zucker rats; it was found that the antagonist decreased the food intake of rats.118 Moreover, this antagonist decreased energy intake, rate of gastric emptying, and body weight gain in ob/ob mice.119
Figure 2. Diagram demonstrating pharmacological tools to enhance or counteract the effects of ghrelin. Synthesis of ghrelin and acylation by GOAT occur in the endoplasmic reticulum. Both acyl and desacyl ghrelin are then secreted into the bloodstream by fusion of secretory vesicles with the plasma membrane. Acyl ghrelin then activates GHSR1a receptors T2R, bitter taste receptor.
Esler et al also showed that the ghrelin antagonist YIL-781 not only reduced fat mass in a mouse model of diet-induced obesity but also directly improved glucose homeostasis by enhancing glucose-stimulated insulin secretion.120 Several compounds have been identified as ghrelin receptor antagonists, including piperidine-substituted quinazolinone derivatives, optimised piperazine-bisamide analogs, and carbohydrazide derivatives. These classes of GHSR1a antagonists could become pharmacological tools for the treatment of obesity, as well as type 2 diabetes and metabolic syndrome. However, long-term human and animal studies are still required to further investigate the beneficial effects of ghrelin antagonists in the context of obesity.
Ghrelin receptor inverse agonists
The ghrelin receptor GHSR1a has a high constitutive activity. It has been proposed that inverse ghrelin receptor agonists could be useful for treating obesity by decreasing this constitutive activity.121 Moreover, it has been hypothesised that the constitutive activity of the receptor may be high between meals, when plasma ghrelin levels are low; hence, it has been suggested that whereas ghrelin receptor antagonists could be used to block the acute preprandial ghrelin signal, inverse ghrelin agonists could block the high constitutive activity.114 The compound [D-Arg1, D-Phe5, D-Trp7,9,Leu11] Substance P was identified as a a low-potency antagonist but a high-potency full inverse agonist on the ghrelin receptor.122 Long-term animal and human studies are necessary to elucidate the beneficial effects of ghrelin receptor inverse agonists in the treatment of obesity.
Ghrelin O-acyltransferase (GOAT) inhibitors
Pharmacological tools have been developed to target the inhibition of GOAT. An example of these is GO-CoA-Tat, which is a peptide-based bisubstrate analog. Barnett et al demonstrated that GO-CoA-Tat potently inhibits GOAT in vitro, in cultured cells, and in mice.123 Moreover, they showed that intraperitoneal administration of GO-CoA-Tat improved glucose tolerance and reduced weight gain in wild-type mice but not in ghrelin-deficient mice. These results indicate that GOAT could be a promising target for the development of anti-obesity and anti-diabetes drugs. In terms of future design of GOAT inhibitors, the results of Yang et al (2008) suggest that GOAT is subjected to end-product inhibition and this inhibition is better achieved with substrates having the octanoyl group attached through an amide linkage rather than the corresponding ester.124
Bitter taste receptors
Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. Jannsen et al (2011) demonstrated that intragastric administration of T2R-agonists increased food intake during the first 30 min in wild-type but not in gust/ and ghrelin receptor knockout mice.125 Moreover, gavage of T2R-agonists increased plasma octanoyl ghrelin levels in wild-type mice but the effect was partially blunted in gust/ mice. The results of this study suggest that activation of bitter taste receptors stimulates ghrelin secretion, meaning that T2R could be a new pharmacological target for the modulation of ghrelin levels.Hormone and Appetite During Puberty Paper
Octreotide is a somatostatin receptor type 2 agonist that is used to treat patients with acromegaly or neuroendocrine tumours. Known side-effects of octreotide include decreased insulin secretion, which can lead to impaired glucose tolerance. Norrelund et al (2002) showed that somatostatin infusion lowered ghrelin levels by 70-80% in healthy volunteers.126 In a pilot study by Haqq et al (2003b), short-term octreotide treatment markedly decreased fasting ghrelin concentrations in children with PWS but did not fully ablate the normal meal-related suppression of ghrelin.127 A 56-week prospective, randomised, cross-over trial by De Waele et al (2008) evaluated whether long-acting octreotide decreases acylated and desacyl ghrelin concentrations, body mass, appetite, and compulsive behaviour towards food in adolescents with PWS.128 It was found that octreotide treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass, appetite or compulsive food-taking behaviour. Based on this evidence, octreotide cannot be currently recommended for the treatment of PWS.128 The authors proposed several possible explanations for these findings. For example, the decrease in circulating ghrelin may be too small to be perceived at the hypothalamic level and translate to clinically-relevant effects, or octreotide may blunt the postprandial decrease in ghrelin concentrations.
Rikkunshito: a ghrelin enhancer
Rikkunshito is a kampo herbal medicine which is widely used in Japan for the treatment of upper gastrointestinal symptoms.129 A study by Matsumura et al (2010) involved administering rikkunshito to healthy volunteers and mice for two weeks and examining the changes in plasma peptide and hormone levels; it was found that rikkunshito increased the plasma acylated ghrelin level in both healthy volunteers and normal mice.130 Apart from stimulating the secretion of ghrelin, rikkunshito can enhance ghrelin’s orexigenic effect by several additional mechanisms; for example, it has been found that rikkunshito increased the reactivity of ghrelin by inhibiting PDE3 activity.131 Examples of indications where rikkunshito use could be beneficial include cisplatin-induced anorexia, anorexia of aging, and stress-related increased or decreased food intake.
Neutralisation of ghrelin
Vaccination against ghrelin could be another strategy to block the effects of ghrelin. Active vaccination of mature rats with ghrelin immunoconjugates led to the production of antibodies directed against acylated ghrelin; the antibody production decreased feed efficiency, relative adiposity, and body weight gain.132 In a study involving normal weight mice and mice with diet-induced obesity, vaccination was shown to be effective in decreasing acute food intake and increasing energy expenditure, but there was no change in body weight over the study span.133 In another study, high-affinity anti-acyl ghrelin-specific monoclonal antibodies were generated; although in a 4-week chronic study the antibodies effectively bound to endogenous acyl ghrelin, long-term administration did not affect food intake or body weight gain in a mouse model of diet-induced obesity.134 Moreover, the development of a ghrelin vaccine in Switzerland has been stopped because of obtaining negative phase IIa results in a study with 111 obese subjects; strong antibody responses to ghrelin were elicited leading to reduced hunger, but there was no significant weight loss.135 The results of these studies suggest that although peripheral neutralisation of ghrelin can suppress appetite stimulated by a transient ghrelin surge, compensatory mechanisms contributing to the regulation of energy balance may prevent long-term effects on body weight. Patients that could benefit by an effective anti-ghrelin vaccine could include individuals with PWS. In obesity, most obese individuals have low ghrelin levels and the vaccine may not be effective on its own for this patient group; instead, an anti-ghrelin vaccine could benefit obese patients enrolling in a diet and exercise program as adjuvant therapy for weight loss and bodyweight control.136
RNA spiegelmers, meaning “RNA mirrors”, are a novel type of ghrelin blocking reagents. Spiegelmers are oligonucleotides synthesised with unnatural L-enantiomers of ribose in the sugar-phosphate backbone, making them stable in vivo. They have been designed to bind specifically and avidly to acylated ghrelin, thus preventing activation of the ghrelin receptor in vitro.114 The spiegelmer NOX-B11-2 blocked ghrelin mediated activation of GH secretagogue receptor 1a in cell culture and also effectively promoted weight loss in diet-induced obese mice.137 Another spiegelmer, NOX-B11-3, effectively blocked the excitatory effect of ghrelin in the medial arcuate nucleus of rats.138 Moreover, i.v. administration of the spiegelmer NOX-B11 efficiently suppressed ghrelin-induced growth hormone release in rats.139 Further investigation is required to elucidate the beneficial clinical effects of spiegelmers, which could be useful to treat diseases with high ghrelin levels and/or severe obesity, such as PWS.Hormone and Appetite During Puberty Paper
Present evidence suggests that ghrelin plays an important role in obesity and eating disorders, as well as in regulating appetite and energy balance in healthy individuals. The effects of ghrelin can be both homeostatic (under the control of circulating hormones acting primarily on the hypothalamus), as well as non-homeostatic involving control of reward-based eating. In pathological states, ghrelin can be lower than normal, as is seen in obese individuals, or can be higher than normal, as has been reported for PWS, anorexia nervosa, bulimia nervosa, and certain types of cachexia.
In the future, the use of ghrelin as a clinical target seems promising. This could involve the use of pharmacotherapies (such as ghrelin administration, ghrelin agonists/antagonists/inverse agonists, GOAT inhibitors), as well as neutralisation of ghrelin (for example, by vaccines and spiegelmers). Further studies and large clinical trials are necessary to fully determine the role that ghrelin can play in future clinical practice.
How will my child change between the ages of 10 and 14?
Throughout our lives we grow and change, but during early adolescence the rate of change is especially evident. We consider 10-year-olds to be children; we think of 14-year-olds as “almost adults.” We welcome the changes, but we also find them a little disturbing. When children are younger, it is easier to predict when a change might take place and how rapidly. But by early adolescence, the relationship between a child’s real age and her* developmental milestones grows weaker. Just how young teens develop can be influenced by many things: for example, genes, families, friends, neighborhoods and values and other forces in society.
As they enter puberty, young teens undergo a great many physical changes, not only in size and shape, but in such things as the growth of pubic and underarm hair and increased body odor. For girls, changes include the development of breasts and the start of menstruation; for boys, the development of testes.
Adolescents do not all begin puberty at the same age. For girls, it may take place anywhere from the age of 8 to 13; in boys, on average, it happens about two years later. This is the time period when students’ physical characteristics vary the most within their classes and among their friends—some may grow so much that, by the end of the school year, they may be too large for the desks they were assigned in September. Others may change more slowly.
Early adolescence often brings with it new concerns about body image and appearance. Both girls and boys who never before gave much thought to their looks may suddenly spend hours primping, worrying and complaining—about being too short, too tall, too fat, too skinny or too pimply. Body parts may grow at different times and rates. Hands and feet, for example, may grow faster than arms and legs. Because movement of their bodies requires coordination of body parts— and because these parts are of changing proportions-young adolescents may be clumsy and awkward in their physical activities
The rate at which physical growth and development takes place also can influence other parts of a young teen’s life. An 11-year-old girl who has already reached puberty will have different interests than will a girl who does not do so until she’s 14. Young teens who bloom very early or very late may have special concerns. Late bloomers (especially boys) may feel they can’t compete in sports with more physically developed classmates. Early bloomers (especially girls) may be pressured into adult situations before they are emotionally or mentally able to handle them. The combined effect of the age on the beginning for physical changes in puberty and the ways in which friends, classmates, family and the world around them respond to those changes can have long-lasting effects on an adolescent. Some young teens, however, like the idea that they are developing differently from their friends. For example, they may enjoy some advantages, especially in sports, over classmates who mature later.
Whatever the rate of growth, many young teens have an unrealistic view of themselves and need to be reassured that differences in growth rates are normal.
Most experts believe that the idea of young teens being controlled by their “raging hormones” is exaggerated. Nonetheless, this age can be one of mood swings, sulking, a craving for privacy and short tempers. Young children are not able to think far ahead, but young teens can and do—which allows them to worry about the future. Some may worry excessively about:
their school performance;
their appearance, physical development and popularity;
the possible death of a parent;
being bullied at school;
not having friends;
drugs and drinking;
hunger and poverty in the country;
their inability to get a good job;
nuclear bombs and terrorists attacks on the country;
the divorce of their parents; and
Many young teens are very self-conscious. And, because they are experiencing dramatic physical and emotional changes, they are often overly sensitive about themselves. They may worry about personal qualities or “defects” that are major to them, but are hardly noticeable to others. (Belief: “I can’t go to the party tonight because everyone will laugh at this baseball-sized zit on my forehead.” Facts: The pimple is tiny and hidden by hair.) A young teen also can be caught up in himself. He may believe that he is the only person who feels the way he feels or has the same experiences, that he is so special that no one else, particularly his family, can understand him. This belief can contribute to feelings of loneliness and isolation. In addition, a young teen’s focus on herself has implications for how she mixes with family and friends. (” I can’t be seen going to a movie with my mother !”)
Teens’ emotions often seem exaggerated. Their actions seem inconsistent. It is normal for young teens to swing regularly from being happy to being sad and from feeling smart to feeling dumb. In fact, some think of adolescence as a second toddlerhood. As Carol Bleifield, a middle school counselor in Wisconsin, explains, “One minute, they want to be treated and taken care of like a small child. Five minutes later they are pushing adults away, saying, ‘Let me do it.’ It may help if you can help them understand that they are in the midst of some major changes, changes that don’t always move steadily ahead.”
In addition to changes in the emotions that they feel, most young teens explore different ways to express their emotions. For example, a child who greeted friends and visitors with enthusiastic hugs may turn into a teen who gives these same people only a small wave or nod of the head. Similarly, hugs and kisses for a parent may be replaced with a pulling away and an, “Oh, Mom!” It’s important to remember, though, that these are usually changes in ways of expressing feelings and not the actual feelings about friends, parents and family.
Be on the lookout for excessive emotional swings or long-lasting sadness in your child. These can suggest severe emotional problems. (For more information, see the Problems section.)
The cognitive or mental, changes that take place in early adolescence may be less easy to see, but they can be just as dramatic as physical and emotional changes. During adolescence, most teens make large leaps in the way they think, reason and learn. Younger children need to see and touch things to be convinced that they are real. But in early adolescence, children become able to think about ideas and about things that they can’t see or touch. They become better able to think though problems and see the consequences of different points of view or actions. For the first time, they can think about what might be, instead of what is. A 6-year-old thinks a smiling person is happy and a crying person is sad. A 14-year-old may tell you that a sad person smiles to hide his true feelings.
The cognitive changes allow young teens to learn more advanced and complicated material in school. They become eager to gain and apply knowledge and to consider a range of ideas or options. These mental changes also carry over into their emotional lives. Within the family, for example, the ability to reason may change the way a young teen talks to and acts around her parents. She begins to anticipate how her parents will react to something she says or does and prepares an answer or an explanation.
In addition, these mental changes lead adolescents to consider who they are and who they may be. This is a process called identity formation and it is a major activity during adolescence. Most adolescents will explore a range of possible identities. They go through “phases” that to a parent can seem to be ever-changing. Indeed, adolescents who don’t go through this period of exploration are at greater risk of developing psychological problems, especially depression, when they are adults.
Just as adults, who with more experience and cognitive maturity can struggle with their different roles, adolescents struggle in developing a sense of who they are. They begin to realize that they play different roles with different people: son or daughter, friend, teammate, student, worker and so forth.Hormone and Appetite During Puberty Paper
They begin to realize that they play different roles with different people: son or daughter, friend, teammate, student, worker and so forth
Young teens may be able to think more like adults, but they still do not have the experience that is needed to act like adults. As a result, their behavior may be out of step with their ideas. For example, your child may participate eagerly in a walk to raise money to save the environment—but litter the route she walks with soda cans. Or she may spend an evening on the phone or exchanging e-mails with a friend talking about how they dislike a classmate because she gossips.
It takes time for young teens and their parents to adjust to all these changes. But the changes are also exciting. They allow a young teen to see what she can be like in the future and to develop plans for becoming that person.
Hormones are chemicals produced by special cells in glands and other organs of the body; most hormones are produced by cells in the endocrine glands. These hormones, which are produced in very small amounts, are released into the bloodstream and travel to the “target organ” or tissue where they exert their effect.
Several hormones are involved in regulating growth. Some act directly on target organs, while others act by triggering the production of other hormones, which activate specific organ functions necessary for growth. This finely tuned system can malfunction in several ways, causing abnormal growth.
The pituitary gland is often called the master gland because it produces several hormones that control the functions of other glands. It is located in the middle of the skull below the part of the brain called the hypothalamus. The pituitary gland has two distinct parts: An anterior (front) lobe and a posterior (rear) lobe. The pituitary gland secretes its hormones in response to chemical messages from the hypothalamus, the part of the brain to which it is connected.
Growth hormone is an anterior pituitary hormone whose main effect is to promote growth of body tissues. Other anterior pituitary hormones affect growth indirectly by working through other glands. These other hormones include:
Thyroid Stimulating Hormone (TSH) – causes the thyroid gland to produce thyroid hormone, which regulates body metabolism and is essential for normal growth.
Adrenocorticotropic Hormone (ACTH) – causes the adrenal glands to produce cortisol (stress hormone) and other hormones that enable the body to respond to stress. Too much cortisol will cause growth failure in a child.
Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) – cause the sex glands (ovaries or testes) to produce sex hormones, which are necessary for adolescent sexual development and the growth spurt that accompanies puberty.
The major hormone produced by the posterior pituitary gland -is called vasopressin, or anti-diuretic hormone (ADH). It controls water output through the kidneys.
CAUSES OF GROWTH HORMONE DEFICIENCY
Growth hormone deficiency may occur by itself or in combination with one or more other pituitary hormone deficiencies. It may be total (no growth hormone is produced) or partial (some growth hormone is produced, but not enough to support normal growth).
Hypopituitarism may be congenital, resulting from abnormal formation of the pituitary or hypothalamus before the child is born, or acquired, stemming from damage to the pituitary or hypothalamus during or after birth. Congenital hypopituitarism is present at birth, although it may not be apparent for many months. Acquired hypopituitarism may become evident any time during infancy or childhood, and may occur after severe head injury or a serious illness such as meningitis or encephalitis. Many cases of acquired hypopituitarism result from a tumor called craniopharyngioma. This tumor may press on the hypothalamus or pituitary, causing one or more hormone deficiencies. Deficiency consists of surgical removal of the tumor, which usually results in permanent hypopituitarism.
Sometimes no cause for hypopituitarism can be identified, or- if a cause is suspected, it may be difficult to prove. Researchers are trying to learn more about the causes of growth hormone deficiency and hypopituitarism.
DIAGNOSIS OF GROWTH HORMONE DEFICIENCY
The child with growth hormone deficiency is often small, with an immature face and chubby body build. The rate of growth of all body parts is slow, so that the child’s proportions remain normal. Intelligence is normal. If the child’s height has been plotted on a growth chart, it will appear to be leveling off and falling away from the child’s established growth curve. If growth failure has been present for a long time, the child may be much shorter than other children the same age. This is why height and weight measurements plotted on a growth chart are so important – the earlier a treatable growth problem is detected, the better the child’s chance of maintaining a normal height throughout childhood and realizing his or her full growth potential.
Any child who is only as tall as children two or more years younger or who falls away from a previously normal growth curve should be evaluated by a doctor. Pediatric endocrinologists are doctors who specialize in treating children with growth and hormone problems. Depending on the situation, the doctor may measure the child over a six to twelve month period in order to accurately determine the child’s growth rate.
The evaluation starts with gathering information on the heights of relatives and the presence of any health problems in the family. A history of early or late puberty (sexual development and growth spurt) in family members should be mentioned. The doctor will want to know about the mother’s pregnancy, labor and delivery. All measurements of the child’s height and weight from birth on should be gathered so the doctor can plot them on a growth chart. The doctor will ask questions about the child’s general health and nutritional state, past illnesses, injuries and stresses.
A thorough physical examination will be performed, and an x-ray of the hand and wrist may be obtained to see how bone development compares to height and chronologic age. A small amount of blood may be drawn to look for evidence of thyroid hormone deficiency and kidney, bone and gastrointestinal (stomach and bowel) diseases. The amount of insulin-like growth hormone-I (IGF-I) in the blood may be measured. IGF-I is the “middle-man” in the growth process. Growth hormone stimulates the liver and other body tissues to produce IGF-I, which then acts as the link between growth hormone in the blood and the machinery inside cells that causes growth. The amount of IGF-I in the blood provides an indirect measure of the amount of growth hormone present.
This simple evaluation often provides the doctor with enough information to identify the cause of the growth problem, or to decide that no growth problem exists. If the doctor suspects that a pituitary problem may exist, further testing is necessary. A series of blood tests can measure concentrations of hormones in the blood and the ability of the pituitary gland to respond to various stimuli. These tests may be done in the clinic or during a brief hospitalization.Hormone and Appetite During Puberty Paper
Growth hormone deficiency is moderately difficult to diagnose because the pituitary gland produces growth hormone in bursts. This means that the level of growth hormone in a single random blood sample is likely to be very low. One way of testing for growth hormone deficiency is to give the child a substance that causes the release of a growth hormone burst in normal children and measure the amount of growth hormone present in several blood samples obtained over a period of time. Since any child may not respond to any given test on a given day, more than one stimulus may be needed to evaluate the child’s ability to produce growth hormone. Several growth hormone stimulators have been identified. These include vigorous exercise and several chemicals and drugs (insulin, arginine, glucagon, L-dopa, clonidine).
Another way of testing growth hormone secretion involves hospitalizing the child and measuring the amount of growth hormone present in blood samples obtained overnight during sleep or even during an entire 24 hour period. Since about two thirds of total growth hormone production occurs during deep sleep, this test provides a better reflection of how much growth hormone the child’s pituitary gland normally produces.
If several tests show that no growth hormone is present or that the amount of growth hormone being produced is not enough to support normal growth, the diagnosis of growth hormone deficiency is established. A great deal of research is being done to develop more accurate and reliable ways of diagnosing growth hormone deficiency. Even the definition of growth hormone deficiency is being revised as researchers learn more about conditions that may cause partial growth hormone deficiency.
TREATMENT OF GROWTH HORMONE DEFICIENCY
Growth hormone deficiency is treated with injections of growth hormone. Most children receive injections daily; others receive it six times a week; and, a few receive it three times a week.* There is usually a prompt increase in growth rate after treatment starts, which may be noticeable to the child and parent in 3 to 4 months. This faster than-normal growth rate slowly declines over time, but it continues to be greater than would occur without treatment. Many parents notice an increase in the child’s appetite and loss of body fat after treatment begins.
The treatment of growth hormone deficiency usually is carried out over several years, until the child achieves an acceptable adult height or maximum growth potential is reached. As with other conditions, children and parents may become impatient to see faster or more impressive results from therapy. They may become discouraged, even when treatment iis going according to plan. It is important to remember that growth is a slow process that is measured over months; children who expect to grow overnight when they start Deficiency will be disappointed. Your child’s doctor will discuss realistic short and long-term expectations of therapy with you.
If testing reveals other hormone deficiencies, medications are available to replace them; thyroid hormone, cortisol and sex hormones can be administered easily when found to be lacking. It is important that these hormones are taken as directed, because normal growth can occur only when all hormones are present in the proper amounts. Good nutrition and adequate rest are important for normal growth in all children.
SOURCES OF HUMAN GROWTH HORMONE
Until recently, the only source of human growth hormone was the pituitary glands of deceased people, obtained at autopsy. In April, 1985, pituitary-derived growth hormone was removed from distribution in the United States and many foreign countries following the deaths of several young adults from a very rare viral disease that may have been transmitted through the pituitary growth hormone they had received many years earlier. Fortunately, the first biosynthetic growth hormone, which is produced using recombinant DNA technology, was in the- final stages of testing and was approved as safe and effective for use in growth hormone deficient children by the Food and Drug Administration in October, 1985. Because this type of growth hormone does not come from human beings, there is little possibility that human diseases can be transmitted through it.
Biosynthetic growth hormone is supplied as a powder in sterile vials. Parents and children are taught how to mix the powder into a solution and administer the injections. Treatment is continued as long as potential for growth exists and the child is responding to therapy. With early diagnosis and a good response to treatment, children with growth hormone deficiency can expect to reach normal adult height.
PSYCHOLOGICAL ASPECTS OF SHORT STATURE
OIur society places great emphasis on height. Children who are short for their age sometimes have problems because playmates and teachers treat them as though they are younger rather than just smaller. Parents tend to do this too, and decrease their expectations of the child. These children then may not act their age because it’s not expected of them. Teasing and name calling may be hard to take. Some of these problems may be helped by frank and open discussion with teachers and classmates.Hormone and Appetite During Puberty Paper
It is very important to provide emotional support for the child with GH deficiency and to emphasize the child’s many good and valuable characteristics, so that the child’s stature does not limit his horizons. More about psychosocial adaptation to short stature can be learned from parents of short children and from your growth clinic doctor, nurse and psychologist.
HOPE FOR THE FUTURE
Biosynthetic growth hormone is available in unlimited quantity for the Deficiency of all growth hormone deficient children. It is possible that substitutes for growth hormone may become available as research continues. These may include growth hormone releasing factor (GHRF), the hypothalamic chemical that directs the pituitary to produce growth hormone, and IGF-I that links growth hormone with linear growth.
Much research is being done to better understand the causes of growth hormone deficiency, and to develop more accurate ways of diagnosing it. Many children with growth hormone deficiency can look forward to reaching normal height as a result of the research that has been done over the years and is continuing today
Normally, the brain produces neurotransmitters (chemicals responsible for how cells communicate in the brain) called endocannabinoids that send signals to control appetite. In this study, the researchers found that when food is not present, a stress response occurs that temporarily causes a functional re-wiring in the brain. This re-wiring may impair the endocannabinoids’ ability to regulate food intake and could contribute to enhanced food drive.
The researchers also discovered that when they blocked the effects of stress hormones in the brain, the absence of food caused no change in the neural circuitry.
Researchers Jaideep Bains, Ph.D. and Quentin Pittman, Ph.D., looked specifically at nerve cells (neurons) in the region of the brain called the hypothalamus. This structure is known to have an important role in the control of appetite and metabolism and has been identified as the primary region responsible for the brain’s response to stress.
Bains explains, “These findings could help explain how the cellular communication in our brains may be overridden in the absence of food. Interestingly, these changes are driven not necessarily by the lack of nutrients, but rather by the stress induced by the lack of food.”
If similar changes occur in the human brain, these findings might have several implications for human health.
“For example, if we elect to pass over a meal, the brain appears to simply increase the drive in pathways leading to increased appetite,” explains Pittman. “Furthermore, the fact that the lack of food causes activation of the stress response might help explain the relationship between stress and obesity.”
These results lay the foundation for future studies to investigate the use of therapies that affect these systems in order to manipulate food intake. They also open the door to studies looking at whether or not the stress brought about by lack of food affects other systems where endocannabinoids are known to play a role.
“One thing we can say for sure, is that this research highlights the importance of food availability to our nervous system. The absence of food clearly brings about dramatic changes in the way our neurons communicate with each other,” says Pittman.
This work was conducted jointly in the labs of Bains and Pittman and the experiments were carried out by Karen Crosby and Wataru Inoue, Ph.D. The research is supported by operating grants from the Canadian Institutes of Health Research (CIHR) and Alberta Innovates- Health Solutions (AI-HS).
Anorexia, or loss of appetite, is when you lose the desire to eat. Mostly seen in women and the elderly, anorexia actually sets in during teenage and adolescence. Loss of appetite may have a cause or may occur without any observed cause. If reduced appetite is because of a medical condition it can be reversed once the condition is treated.
Loss of appetite as such is not life threatening, but it can be a symptom of an underlying condition such as cancer, so it is best not to ignore chronic or prolonged loss of appetite.
How do we lose our appetite?
Proper release of hormones and enzymes is very important for our physical and mental health. And it is the brain that controls the release of these hormones and enzymes. For example, a part of the brain called hypothalamus controls the functions related to appetite and satiety. Similarly, our appetite is regulated by hormones leptin and ghrelin. When the levels of leptin increase in the blood due to certain triggers, the hypothalamus reduces appetite, and when the levels of ghrelin increase in the blood, the hypothalamus signals the triggering of appetite.
Depression and anxiety
‘Nothing mitigates the throes of depression like a steaming plate of spaghetti and meatballs with marinara sauce and grated parmesan cheese, with a good fresh bread to wipe up.’ – Paul Clayton
But all people with depression may not agree. Some people lose their appetite when they are suffering from depression. People with depression or anxiety disorder tend either to binge eat or lose their appetite for food.
It has long been known that mood-related chemicals such as serotonin are associated with depression and anxiety disorders. It is also known that increased serotonin lead to reduced food intake. But how serotonin reduces appetite is not exactly known. One theory is that serotonin reduces the release of peptide AgRP which is a naturally made appetite stimulant, and increases the release of alpha-MSH, an appetite suppressing peptide. Alpha-MSH in turn activates melanocortins that influence weight regulation and reduce appetite.
Another theory is that chemical imbalance in the brain is caused by presence of excessive levels of monoamine oxidase A (MAO-A). This enzyme leads to greater break down of key chemicals like serotonin. Scientists believe that individuals with depression lose chemicals like serotonin and dopamine at different rates based upon monoamine transporter density. Monoamine transporter removes monoamines from the active site. So, if monoamine transporter is more dense, it means MAO-A is removed at higher level, resulting in increased serotonin levels leading to loss of appetite. On the flip side, less monoamine transporter means less serotonin levels leading to overeating.
When you encounter a stressful event, your body adopts certain coping strategies by diverting its resources appropriately to assist in dealing with the stressor. When you are stressed your body goes into fight-or-flight response flooding the system with stress hormones such as norepinephrine and cortisol that help boost your defense mechanism.
The hypothalamus releases a corticotropin-releasing hormone (CRH), which along with other hormones inhibit certain protein particles responsible for stimulating feeding behaviour. This way the digestive process comes to a stop so that your body doesn’t waste energy through digestive processes and the energy can be used to counter the stressor.
Many people who have cancer or are undergoing cancer treatment lose their desire to eat. Although scientists are not sure what exactly causes loss of appetite in cancer patients, they think it the growth and spread of tumour cells set off the metabolic disturbance and the neuro-hormonal signaling (CRH, ghrelin, etc.) pathways in the patient leading to anorexia.Hormone and Appetite During Puberty Paper
Loss of appetite can also occur because of secondary causes such as –
Depression and anxiety
Less physical activity
Unpleasant odours or sights
Nausea and vomiting
Tuberculosis, an infectious lung disease caused by bacteria Mycobacterium tuberculosis, has loss of appetite as one of its main symptoms. Here too, researchers are not sure of the mechanism of how anorexia occurs in people with tuberculosis. However, some studies found that leptin levels, once thought to be the main cause of anorexia in tuberculosis, actually do not in any way influence the onset of anorexia in TB patients. Scientists think other appetite regulating hormones are altered in TB. For example, they found that up-regulation of plasma peptides (PYY) resulted in suppression of appetite.
3. Other physical illness
Whatever the mechanism of anorexia, other diseases such as HIV, hepatitis, thyroid problems, chronic liver disease, chronic kidney failure, heart failure, too can cause loss of appetite.
Anorexia in pregnancy and post-pregnancy
Some women lose their appetite during pregnancy or soon after they give birth.
‘What’s Wrong With Me? I was a healthy person before I had kids, seems like they kind of wrecked me in many ways. The biggest thing that happened was after my son was first born. I just had no interest in food!! I mean, I look at it, I feel ill. I eat it, I feel ill. I can’t force myself to eat, and I just don’t enjoy it anymore. It’s like my taste buds are bored and just don’t want to taste food anymore.’
This is how Rita felt after giving birth to her son. She was diagnosed with anorexia.
Scientists believe there can be a number of reasons for anorexia after giving birth.
Caring for new born baby can be stressful and lead to sleep disorders and eating disorders like anorexia.
Increasing concern over body image (shape and weight) in the first 6 months after giving birth is almost normal for women. Increased body fat and loss of abdominal muscles can cause some women to resort to eating disorder behavior such as anorexia.
Post-partum depression during perinatal period too can cause loss of appetite.
Babies born to mothers with anorexia may have nutritional deficiencies that can affect their physical and cognitive abilities. So, it is important that you consult your doctor as soon as you notice that you are losing appetite.
Loss of appetite in children and adolescents
When it comes to children and adolescents, a few types are more predisposed to loss of appetite than the others:
Children and teens coming from families that are too rigid, overly critical, intrusive, or overprotective.
Adolescents coming from families that have weight problems, physical illness, and /or suffering from mental disorders such as depression and substance abuse.
Adolescents with more concern for appearances and harbour a negative self image.
Sometimes, they may also be genetically disposed to anorexia.
Certain neurochemical and developmental factors too can cause anorexia in children and adolescents.
Loss of appetite in elderly
Elderly people may lose their appetite from slightly different reasons.
Medical causes include use of certain drugs, gastrointestinal and metabolic disorders, infections or heart disease.
Social factors such as loneliness, depression, and isolation, may also greatly reduce the elderly person’s interest in food.
Self-consciousness because of hearing or visual impairment is another factor that can cause loss of appetite.Hormone and Appetite During Puberty Paper
Know that anorexia is associated with low bone mineral density that leads to increased risk of fracture and bone disorders such as osteoporosis. It can destroy your kidneys and your heart. Anorexia can also lead to brain dysfunction and other body disorders. Get medical help, don’t ignore the condition!Hormone and Appetite During Puberty Paper