A leptin antagonist hormone, ghrelin is mainly used to send hunger signals to the brain to promote the absorption of food. However, it can be a problem in the event of a malfunction.
What is ghrelin?
Ghrelin is a hormone produced by the stomach and pancreas that stimulates the appetite. It is an antagonist to leptin, whose role is to control the body’s satiety effect, but the two hormones act in a complementary way to regulate an individual’s weight (1). This molecule is also called the “hunger hormone” and is of major importance.
When it is functioning normally, it is found at a high level just before meals, but its level should drop as the stomach fills up and leptin levels rise.
In people who do not have any dysfunction in hormone levels, hormones work in a complementary way. After eating too much for some time, most individuals will tend to naturally regulate the amount of food swallowed to regulate their weight. However, certain malfunctions can disrupt this regulatory system and lead to obesity.
Ghrelin dysfunction in obese subjects
The causes of obesity cannot always be identified. However, in some cases, hormonal or physiological dysfunction may be involved. A study carried out in 2013 revealed that particular antibodies had been found in obese patients with normal ghrelin levels (2).
This study showed that these immunoglobulins could recognize a hunger hormone but protected it instead of promoting its rapid degradation in the blood. Thus, more of it can be transported to the brain and inhibits the action of the satiety hormone. It is this dysfunction that causes some cases of hyperphagia.
Some people may also experience an increase in hormone levels. This is particularly the case in children with Prader-Willi syndrome (3), a disease that leads to growth hormone deficiency and very significant hyperphagia causing childhood obesity. However, ghrelin may also be present in abnormal amounts in patients suffering from anorexia nervosa. In this case, it is only present to try to correct the situation.
The influence of ghrelin on the brain
During a normal day, ghrelin is produced in sufficient quantities and brought to the brain, where neurons send signals to the hypothalamus to encourage food intake. The neurons then send signals to the hypothalamus to encourage the ingestion of food. The action of the hormone is then compensated for by other mechanisms that interact with the brain to create the sensation of satiety.
The hunger hormone is very sensitive to external dysfunctions. The presence of antibodies can alter its quantity, as well as external environmental factors. However, depending on the number of hormones sent to the brain, the hypothalamus will react differently by secreting various molecules. Among them is orexin, which is a molecule that promotes overeating, mainly hyperphagia.
The strong influence of this hunger hormone on the brain has consequences on how to gain or lose weight. Once the problem has been identified, certain diets should be avoided at all costs to help people regain normal weight. However, many popular diets work against sustainable weight loss in the context of hormonal dysfunction.
How does hunger hormone change during a diet?
For several years, a team working at the University of Southern California studied the evolution of ghrelin levels in the body at different stages of a diet (4). The main information that emerged from this study is the significant increase in the level of the hunger hormone after a period of fasting that is a little too long.
The team conducted its experiment on rats that were only allowed to eat for four hours, with the obligation to fast for the rest of the day. After fasting, when food was perceived by the rat, the hormone was sent to the brain, where the hypothalamus produced large amounts of orexin, promoting excess food intake.
This mechanism has significant usefulness in times of famine by allowing the body to absorb an abnormal number of calories over a given time to cope with a fast, but with the abundance of food, this mechanism has become a problem for some people. This is also the reason why it is strongly discouraged to follow a diet involving excessive fasting if one wants to lose weight in the long term.
Also read: Do hormones make you fat?
Sources and References
(1) Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ, A. INUI, A. ASAKAWA, C. Y. BOWERS, G. MANTOVANI, A. LAVIANO, M. M. MEGUID, and M. FUJIMIYA, The FASEB Journal, 2004 18:3, 439-456 Published on 1 March 2004. www.fasebj.org/doi/10.1096/fj.03-0641rev
(2) Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans, Takagi K1, Legrand R, Asakawa A, Amitani H, François M, Tennoune N, Coëffier M, Claeyssens S, do Rego JC, Déchelotte P, Inui A, Fetissov SO, Nature Communications (4), N°2685 (2013) www
(3) Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome
Haqq AM1, Farooqi IS, O’Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, LaFranchi SH, Purnell JQ, J Clin Endocrinol Metab. 2003 Jan;88(1):174-8.
www.ncbi.nlm.nih.gov/pubmed/12519848(4) Hippocampus ghrelin signaling mediates appetite through lateral hypothalamic orexin pathways, T