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 adaption to changing environments and the process of learning.

Forms

Ghrelin exists in an inactive and an active (octanoylated) form (see Hexatropin).

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 circulatory 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).

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.

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.

External links

ColoState.edu - 'Ghrelin'
InfoBiogen.fr - 'Ghrelin/MTLRP' (motilin-related peptide)
NeuroEndo.org.uk - 'Ghrelin: A newly discovered hormone', Dr. Suzanne L. Dickson, University of Cambridge (June 14, 2005)
Recorded interview with Dr. Robert Rutledge discussing Ghrelin and the impact on the obesity epidemic on archived radio show
ScienceNews.org - 'Still Hungry? Fattening revelations—and new mysteries—about the hunger hormone', Janet Raloff, Science News, vol 167, no 14, p 216 (April 2, 2005)