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. Plasma concentrations of ghrelin increase progressively before meals and decrease after meals. It is considered the counterpart of the hormone leptin, produced by adipose tissue, which suppresses appetite. Ghrelin also stimulates the secretion of growth hormone from the anterior pituitary gland.

Receptors for ghrelin are expressed in several areas of the central nervous system, but at particularly high densities 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). There is also evidence that ghrelin may also be made by a small population of neurons in the arcuate nucleus.

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 [1]. 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.

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.

References

• Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, Smith RG, Cunningham GR, Marcelli M. "Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia." J Clin Endocrinol Metab 2005;90:2920-6. PMID 15713718.
• Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. "Ghrelin is a growth-hormone-releasing acylated peptide from stomach." Nature 1999;402:656-60. PMID 10604470.
• Yildiz BO, Suchard MA, Wong ML, McCann SM, Licinio J. "Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity." Proc Natl Acad Sci U S A 2004;101:10434-9. PMID 15231997.
• Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. "Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery." New England Journal of Medicine 2002;346:1623-1630.
• Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJW. "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake." Science 2005;310:996-999. PMID 16284174.