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 Ghrelin & Leptin     
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How The Hormones Ghrelin and Leptin Affect Appetite

These three hormones, orexin, gherlin and leptin, act on your brain to normalize your drive for food. In this way your body responds appropriately with hunger for breakfast. Breakfast is the combination of two words, “break” and “fast”.

While ghrelin is an appetite-stimulating peptide, leptin is an appetite-suppressing one. Ghrelin, secreted from the stomach, particularly influences the metabolism of fat tissue by promoting its storage during hard times. Leptin and ghrelin function interdependently in healthy humans.

The world leptin means “full” in Greek. Leptin is produced in the fat cells and released in the brain. Leptin gives us a feeling of satisfaction. While ghrelin enhances appetite, leptin acts as a satiety signal to diminish it. Yet, it’s not that simple. There are multiple receptors in fat cells. These produce other hormones, which can interfere in our response to food intake. A balance exists between your fat cells and your appetite.

The discovery of ghrelin at the end of the last century, definitely contributed to the understanding of the regulation of appetite and eating behavior. Ghrelin, consisting of 28 amino acids, was first identified in the stomach in 1999. It is produced in glandular cells of the stomach lining, but is also found in the pituitary, the hypothalamus and the pancreas.

According to ongoing research, ghrelin has multiple biological roles: for example, ghrelin stimulates the release of growth hormone and also induces a rise in the concentration of other hormones including cortisol. Through these multiple mechanisms ghrelin can accelerate food intake boosting weight.

High levels of blood sugar trigger this overeating behavior. In other words, binge eating or out-of-control feeding,  called hyperphagia,  is associated with a malfunction in the brain’s hunger signals. The level of ghrelin depends on the state of nutrition and hydration of an individual. So its effect does not end with hunger, it affects thirst as well.

Ghrelin fluctuates both before and after food intake with an increase prior to a meal and a decrease afterwards. Ghrelin also regulates water and fluid intake, so if you drink a glass of water when you are hungry, ghrelin signals can be satisfied and weakened slightly. This provides a simple way to control your hunger. One glass of water before every meal decreases the amount you will eat by at least 8 ounces and suppresses ghrelin.

Slim women have learned to lower their ghrelin level, but these amounts rise immediately with diet-induced weight loss. Yes, thin people do not diet for that very reason. If they did, they would start to gain weight. The more a person diets, the hungrier they get. It is almost as if semi-starvation triggers gherlin to increase. This may be part of the reason that we regain weight lost by dieting and then some. The secret is to stop dieting.

In addition to stimulating GH secretion, ghrelin affects your stomach acid secretion and how smoothly the food moves along your gut. This function called intestinal motility is damaged in both constipation and diarrhea. A condition called “irritable bowel syndrome” may be nothing more than a ghrelin imbalance. More research is needed.

Ghrelin induces other metabolic actions such as spikes in blood sugar, called the  hyperglycemic effect. Therefore modified fasting, which decreases ghrelin secretion and increases leptin, may provide an effective technique for treating obesity.

As your circulating ghrelin adapts to weight loss, hunger dissipates. I have to remind you however, that ghrelin levels rise with dieting so that the more you restrict food intake, the hungrier you get. But how can fasting help? There is an interesting slant to this answer.

The more you restrict your calories, the lower the baseline for ghrelin. Ghrelin levels tend to decrease naturally after you fast for a few days. That means that after fasting for more than 48 hours, your hunger diminishes.

By decreasing the inflow of food and reducing caloric intake for as little as a few days, you can lessen the attendant cravings. This is an important tip to remember. When you are gaining weight, fast for two or three days and you will become less hungry and regain some control. 

Fortunately, through the help of certain medications, you may be able to decrease ghrelin for a long time. Lowered levels of ghrelin will not only decrease your appetite, but also help you to develop a leaner body. Another interesting result is that as ghrelin diminishes, growth hormone rises.

Increased growth hormone shifts your body fat to lean muscle while lowering blood pressure and cholesterol levels. In this case, I am referring to natural growth hormone, which increases after you have a good night’s

An increase in the ghrelin level boosts hunger over the long run. For this reason within a year of losing over ten pounds, almost 95 percent of dieters regain the weight they lost.

Another way of putting it is that weight loss causes changes in appetite and energy expenditure that eventually promote weight regain to the original set point. This fact is well known to most dieters, who inevitably reclaim all their lost weight within a year because they were so hungry all the time. What can a well-regimented repeat dieter can do besides get fatter and fatter with each diet?

Stop dieting! By now you have discovered that the desire for food is controlled by complex interactions between hunger/satiety and caloric or energy requirements. By slowing down digestion and increasing the length of time food stays in the stomach, it is possible to maintain equilibrium between ghrelin and leptin. Through fasting and chewing your food slowly you can suppress ghrelin and hunger at its origin.

Another tip involves adding soluble fiber and eating large amounts of complex carbohydrates. You can feel full longer and slow down the passage of food down your intestine. Slow digestion abolishes hunger by providing a shortcut to the long-term satiety center in your hypothalamus.

Selecting high quality protein, low fat foods that require slow digestion while chewing food very unhurriedly and thoroughly, signals your brain that you are getting satisfied. Finally you can stop eating after the meal is over.

Let us have a quick review: the hormone leptin acts in your brain to adjust the expression of several chemicals from your hypothalamus. These chemicals maintain the balance when leptin from your fat cells, alerts your brain that you have had enough to eat. What happens next is that you become less hungry.

The transmitter that maintains the relationship between fat tissue and the brain is known as an endocannabinoid, which translates the information as to the amount of body fat needed to deal with energy requirement. Think of leptin as a fat cell thermostat, active in the fat depots, while monitoring your energy maintenance system.

Leptin does this by modifying the appetite-regulating chemicals called peptides, which are either appetite stimulating (orexigenic) or appetite suppressing (anorexigenic). Leptin also suppresses a liver enzyme that converts unsaturated fats into monounsaturated fats burning fat as energy.

The balance and communication between these two systems sets a limit on food intake and growth hormone release. An impairment of this equilibrium results in disorders of feeding behavior such as weight gain or weight loss (cachexia). Neither is very desirable. If leptin is so useful, what about getting leptin shots?

Unfortunately, doctors can’t give someone a leptin shot to make them stop eating, since in severely obese people, unlike mice, hormones seem to work differently. In genetically altered mice, without the receptor for leptin, injecting leptin will only partially correct the defect reversing their obesity. This indicates that other factors play supporting roles. Leptin corrects insulin resistance, or diabetes, in mice that lack fat tissue (a condition called lipodystrophy). Scientists have tried leptin replacement therapy in lipodystrophic humans with good results.

People who are out of control with their eating may have become leptin-insensitive. In reality, when they are full, they don’t stop eating. They have become resistant to their own leptin effects.  If leptin is not working then the enzyme mentioned earlier rises and more fat is stored in the liver. Women seem to suffer from this problem more than men.   But remember that most of these genetic effects have been bred into our species over time. You can modify your genetics.

Hellstrom PM, et al. Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects. Br J Nutr. 2004 Aug;92 Suppl 1:S47-57.

Broglio F, et al.  J Clin Endocrinol Metab. 2001 Oct;86(10):5083-6. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans.    

Tritos NA, Maratos-Flier E. Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone. Neuropeptides. 1999 Oct;33(5):339-49

Di Marzo V, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001 Apr 12;410(6830):822-5

Oral EA, Simha V, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002 Feb 21;346(8):570-8. elif_arioglu@nih.gov

Chan JL, et al. Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects. J Clin Endocrinol Metab. 2004 Jan;89(1):335-43.





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