Ghrelin: The "Hunger Hormone"

Ghrelin, the "hunger hormone", also known as lenomorelin (INN), is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract which functions as a neuropeptide in the central nervous system. Besides regulating appetite, ghrelin also plays a significant role in regulating the distribution and rate of use of energy.

When the stomach is empty, ghrelin is absorbed. When the stomach is stretched, secretion stops. It acts on hypothalamic brain cells both to increase hunger, and to increase gastric acid secretion and gastrointestinal motility to prepare the body for food intake.

The receptor for ghrelin, the ghrelin/growth hormone secretagogue receptor (GHS-R), is found on the same cells in the brain as the receptor for leptin, the satiety hormone that has opposite effects from ghrelin. Ghrelin also plays an important role in regulating reward perception in dopamine neurons that link the ventral tegmental area to the nucleus accumbens (a site that plays a role in processing sexual desire, reward, and reinforcement, and in developing addictions) through its colocalized receptors and interaction with dopamine and acetylcholine. Ghrelin is encoded by the GHRL gene and is presumably produced from the cleavage of the prepropeptide ghrelin/obestatin. Full-length preproghrelin is homologous to promotilin and both are members of the motilin family.

Unlike the case of many other endogenous peptides, ghrelin is able to cross the blood-brain-barrier, giving exogenously-administered ghrelin unique clinical potential.

Ghrelin has been linked to inducing appetite and feeding behaviors. Circulating ghrelin levels are the highest right before a meal and the lowest right after. Injections of ghrelin in both humans and rats have been shown to increase food intake in a dose-dependent manner. So the more ghrelin that is injected the more food that is consumed. However, ghrelin does not increase meal size, only meal number. Ghrelin injections also increase an animal's motivation to seek out food, behaviors including increased sniffing, foraging for food, and hoarding food. Body weight is regulated through energy balance, the amount of energy taken in versus the amount of energy expended over an extended period of time. Studies have shown that ghrelin levels are negatively correlated with weight. This data suggests that ghrelin functions as an adiposity signal, a messenger between the body's energy stores and the brain. 

Ghrelin and Obesity

• Ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals, suggesting that ghrelin does not contribute to obesity, except in the cases of Prader-Willi syndrome-induced obesity, where high ghrelin levels are correlated with increased food intake. However, it is also found that consumption of food for pleasure increased peripheral levels of both ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in healthy humans, and this hedonic eating influences food intake and, ultimately, body mass.
• Those with anorexia nervosa have high plasma levels of ghrelin compared to both the constitutionally thin and normal-weight controls.
• The level of ghrelin increases during the time of day from midnight to dawn in thinner people, which suggests there is a flaw in the circadian rhythm of obese individuals.
• Ghrelin levels reflect release in a circadian rhythm which can be interrupted by exposure to light at night.
• Short sleep duration may also lead to obesity, through an increase of appetite via hormonal changes.
• Lack of sleep increases ghrelin, and decreases leptin, both effects producing increased hunger and obesity.
• Ghrelin levels are high in patients with cancer-induced cachexia [a wasting disease].

Medical Notes

Gastric bypass surgery not only reduces the gut's capacity for food but also dramatically lowers ghrelin levels compared to both lean controls and those that lost weight through dieting alone. However, studies are conflicting as to whether or not ghrelin levels return to nearly normal with gastric bypass patients in the long term after weight loss has stabilized. Bariatric surgeries involving vertical sleeve gastrectomy reduce plasma ghrelin levels by about 60% in the long term.

Ghrelin is not FDA approved for any indication.

In rodents and pigs, an anti-obesity vaccine has been developed: it blocks the ghrelin receptor.

Ghrelin plasma concentration increases with age and this may contribute to the tendency for weight gain as people age.

Future Clinical Uses

• Synthetic ghrelin administration for cachexia of any cause and for hemodialysis patients is being investigated.
• Ghrelin suppresses seizures in animal models and is being investigated.
• Ghrelin is a gastric pro-kinetic and may be useful in the treatment of gastroparesis.

https://en.wikipedia.org/wiki/Ghrelin