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How Hormones Control Weight Management

4/20/2022

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Weight Management is not about calories in and calories out. It can be far more complicated. Two hormones that play a crucial role in controlling when we eat but also when we don't are Ghrelin and Leptin. Working together they tell us when we're hungry and when we're not. Each are controlled by a variety of physical and psychological factors.   
German researchers have suggested that ghrelin levels play a big role in determining how quickly hunger comes back after we eat. Normally, ghrelin levels go up dramatically before you eat; this signals hunger. They then go down for about three hours after the meal.

But some researchers believe that ghrelin is not as important in determining appetite as once thought. They think that its role in regulating body weight may actually be a more complex process.
What We Know About Leptin -- the appetite suppressor -- appears to be the bigger player in our bodies' energy balance. Some researchers think that leptin helps regulate ghrelin.
Leptin helps signal the brain that the body has enough energy stores such as body fat. But many obese people don't respond to leptin's signals even though they have higher levels of leptin.
In general, the more fat you have, the more leptin is in your blood. But the level varies depending on many factors, including when you last ate and your sleep patterns.
A study showed that rats that were given doses of leptin ended up eating less, but this effect lasted only about two weeks. It seems that the rats developed a resistance to leptin's appetite-cutting effects.
How to Control Hunger HormonesAre there ways to control our "hunger hormones," and thus rein in our appetites? Possibly -- by avoiding high-fat foods.
When we eat, messages go out to various parts of our bodies to tell us we've had enough. But when we eat fatty meals, this system doesn't work as well, says Dallman. Eating fat tends to lead to eating more calories, gaining weight, and storing fat, Dallman says. Researchers have seen some of these effects after only three days of a high-fat diet.
But researchers have shown that either a diet rich in either "good" carbohydrates (like whole grains) or a diet high in protein suppresses ghrelin more effectively than a diet high in fat.
Something that might help (and certainly won't hurt) is to get enough sleep! In a study of 12 young men, sleep deprivation was associated with an increase in ghrelin levels, appetite, and hunger compared with when they slept 10 hours a night.
All in all, this adds to the huge amount of evidence showing that avoiding a high-fat diet is one of the keys to maintaining a healthy weight.
Leptin inhibits ghrelin in two ways; it reduces ghrelin secretion by gastric cells, and suppresses the expression of ghrelin receptors in the NPY system, therefore preventing the stimulation of feeding behaviors by the latter. This effect is postulated to constitute the major feedback loop between the organs of eating and the hypothalamus which maintains body weight.
When this loop is disrupted at any point, either in terms of timing, duration, or magnitude of feedback impulse signalling, hypothalamic loss of feeding is lost, resulting in obesity. Leptin also increases the rate of thermogenesis and thus promotes weight maintenance.
Ghrelin, on the other hand, stimulates feeding and results in obesity. It is produced in the stomach and also in the hypothalamic subparaventricular zone, which has an appetite-stimulant action. Ghrelin levels rises before a meal, and goes down after meals.
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Moreover, ghrelin levels fluctuate in accordance with changes in energy reserves in the body. Thus ghrelin is episodic in secretion, but the amplitude depends upon the feeding status. This hormone is also involved in the short-term regulation of human appetite.
Experimentally, even when the same type of diet is fed to different rodents, two categories are rapidly formed: the first is obesity-prone and starts to put on weight rapidly, whereas the second group shows a static weight. This can be explained by the fact that the first group alone shows high leptin levels, with low ghrelin levels, possibly caused by the former. Conversely, the other group has no alteration in the secretion of both hormones.
Hypothalamic Restraint by LeptinIn another study, leptin lowering was associated with high levels of ghrelin secretion, but there was a centrally-operating suppression of the expected appetite drive despite increased ghrelin. Ghrelin secreted in the stomach mucosa circulates to the brain and crosses the blood-brain-barrier. It acts together with locally secreted ghrelin in the hypothalamus to stimulate the NPY and other neurons in the ARC-PVN nucleus to stimulate appetite. This can be inhibited by Y1 receptor antagonists acting on the NPY neurons.
Leptin acts to reduce the synthesis, release, and biological actions of NPY in the ARC-PVN neuronal system via long leptin receptor activation. Yet leptinopenic mice (i.e. those with low levels of leptin) failed to develop a good appetite, though their ghrelin levels rose. Thus the hypothalamic restraint exercised by leptin overrides even a strong peripheral afferent signal by ghrelin.
Actions of GhrelinThere are several notable actions that ghrelin has on a human body:
  • It regulates the blood glucose levels through reduced insulin secretion and by regulating the synthesis and breakdown of glucose and glycogen
  • It reduces heat production to conserve energy
  • It reduces sympathetic activity
  • It promotes the differentiation and fusion of muscle fibers
  • It plays a role in regulating bone growth through osteoblast differentiation and proliferation, a role in bone protection, and has an opposing role to leptin in bone metabolism
  • It is also highly expressed in metastatic cancer cells
When the body is in positive energy balance, ghrelin levels go down, and vice versa in cases of fasting or anorexia nervosa. Leptin does exactly the opposite; however, it is not clear whether the primary stimulus is the calorie deprivation or the lower energy stores.
In the anorexic eating disorders, the ghrelin levels are chronically raised, which may be due to the negative state of the body’s energy, and are meant to stimulate the appetite to increase body fat percentage. Nevertheless, it may also mean that such patients are unresponsive to ghrelin.


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