Ghrelin

Ghrelin is a hormone produced by P/D1 cells lining the fundus of the human stomach that stimulate appetite (Bowers, et al). In rodents, X/A-like cells produce ghrelin. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone leptin, produced by adipose tissue, which induces satiation when present at higher levels. Ghrelin also stimulates the secretion of growth hormone from the anterior pituitary gland.

Receptors for ghrelin are expressed by neurons in the arcuate nucleus and the ventromedial hypothalamus. The ghrelin receptor is a G-protein coupled membrane receptor, formerly known as the GHS receptor (growth hormone secretagogue receptor). Ghrelin is also made by a small population of neurons in the arcuate nucleus. Ghrelin plays a significant role in neurotrophy, particularly in the hippocampus, and is essential for cognitive adaptation to changing environments and the process of learning.

Forms
Ghrelin exists in an inactive (pure peptide) and an active (octanoylated) form (see Hexatropin). Other side chains than octanoyl were also observed.

Role in disease
Ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals. Yildiz et al (2004) found that the level of ghrelin increases during the time of day from midnight to dawn in thinner people, suggesting a flaw in the circadian system of obese individuals. Professor Cappuccio of the University of Warwick has recently discovered that short sleep duration may also lead to obesity, through an increase of appetite via hormonal changes. Lack of sleep produces Ghrelin, which stimulates appetite and creates less leptin which, amongst its many other effects, suppresses appetite.

Those suffering from the eating disorder anorexia nervosa appear to have high plasma levels of ghrelin. Ghrelin levels are also high in patients who have cancer-induced cachexia (Garcia et al, 2005).

Prader Willi Syndrome is another example of high levels of Ghrelin, but here the ghrelin level are associated with high food intake.

At least one study found that gastric bypass surgery not only reduces the gut's capacity for food, but also dramatically lowers ghrelin levels (Cummings et al, 2002).

Animal models indicate that ghrelin may enter the hippocampus from the bloodstream, enhancing learning and memory. It is suggested that learning may be best during the day and when the stomach is empty, since ghrelin levels are higher at these times.

Relation to obestatin
Obestatin is a hormone that was found, in late 2005, to decrease appetite. Both obestatin and ghrelin are encoded by the same gene; the gene's product breaks apart to yield the two peptide hormones (Zhang et al 2005). The purpose of this mechanism is unknown.

History and name
The discovery of ghrelin was reported by Masayasu Kojima et al in 1999. The name is based on its role as a growth hormone-releasing peptide, with reference to the Proto-Indo-European root ghre, meaning to grow.

Anti-Obesity Vaccine
Recently Scripps research scientists have developed an anti-obesity vaccine, which is directed against the hormone ghrelin. The vaccine uses the immune system, specifically antibodies, to bind to selected targets, directing the body's own immune response against them. This prevents ghrelin from reaching the central nervous system, thus producing a desired reduction in weight gain.