Ghrelin

Ghrelin is a small peptide hormone, twenty-eight amino acids in length, secreted chiefly by specialized endocrine cells of the stomach lining, with smaller amounts made in the small intestine, pancreas, brain, and other tissues ^[1][2]. It circulates in the blood and signals to the brain and body about energy status, and because it increases the drive to eat it is often called the hunger hormone ^[2]. Its concentration follows a daily and meal-related rhythm, climbing during fasting and just before a meal and falling once food has been eaten.

The hormone was discovered in 1999 by Masayasu Kojima, Kenji Kangawa, and colleagues, who purified it from stomach tissue while searching for the natural ligand of a previously identified receptor, the growth hormone secretagogue receptor ^[1]. They named it ghrelin, drawing on an ancient root meaning to grow, in recognition of its ability to release growth hormone. A defining feature of the hormone is that it needs a fatty-acid modification to work: an eight-carbon octanoyl group is attached to the serine at position three by the enzyme ghrelin O-acyltransferase, and this acylation is essential for the peptide to activate its receptor ^[1][2]. Most of the ghrelin circulating in blood is in fact unacylated, a form with different and more limited signaling activity.

Ghrelin acts on the growth hormone secretagogue receptor type 1a, which is present in the hypothalamus and pituitary as well as in the vagus nerve and the gastrointestinal tract ^[2]. Through these sites it prompts the pituitary to release growth hormone, encourages appetite and food intake, favors the storage of fat, and helps regulate body weight over the long term ^[1][2]. It also speeds the emptying and motility of the stomach, influences insulin and glucose handling, and has been linked to sleep, reward-seeking behavior, taste, learning, and memory ^[2]. Studies have shown that ghrelin levels rise after diet-induced weight loss, consistent with a role in the body's defense of its weight, whereas gastric bypass surgery is followed by markedly reduced ghrelin, which may contribute to the appetite changes seen after that operation ^[3].

Because of these actions, ghrelin and synthetic compounds that imitate or block it have been explored for conditions involving appetite and body weight, including the wasting syndrome known as cachexia, poor appetite, and disorders of gastric emptying, as well as, in the opposite direction, obesity ^[2]. Ghrelin itself is a natural hormone rather than an approved medicine, though related agents acting at its receptor have been developed. Its wide range of effects continues to make it a subject of active study in metabolism and neuroscience ^[2].

Exogenous ghrelin or strong mimetics increase hunger, which can be counterproductive for fat loss, and raise GH and IGF-1, which carries the usual concerns about water retention, insulin resistance and joint discomfort. Native ghrelin is rarely used directly; the mimetics have their own side-effect profiles. Anyone with cancer risk should be cautious given GH/IGF-1 involvement.