Ghrelin: a hormone regulating food intake and energy homeostasis

Abstract

Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasis. The ghrelin gene is composed of four exons and three introns and renders a diversity of orexigenic peptides as well as des-acyl ghrelin and obestatin, which exhibit anorexigenic properties. Ghrelin stimulates the synthesis of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus neurons of the hypothalamus and hindbrain, which in turn enhance food intake. Ghrelin-expressing neurons modulate the action of both orexigenic NPY/AgRP and anorexigenic pro-opiomelanocortin neurons. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acids, and this appears to be the molecular signal for the expression of NPY and AgRP. Recent data suggest that ghrelin has an important role in the regulation of leptin and insulin secretion and vice versa. The present paper updates the effects of ghrelin on the control of energy homeostasis and reviews the molecular mechanisms of ghrelin synthesis, as well as interaction with GHS receptors and signalling. Relationships with leptin and insulin in the regulation of energy homeostasis are addressed.

Circulating obestatin levels and the ghrelin/obestatin ratio in obese women

“…The negative correlation of the ghrelin/obestatin ratio with insulin may be consistent with the putative negative regulatory effect of insulin on circulating ghrelin (31). Insulin excess, in fact, has been proven to decrease ghrelin concentrations in both rodents (32) and humans (33,34).…”

Adaptation of ghrelin and the GH/IGF axis to high altitude

“…Most importantly, weight loss associated with an anorexic condition has an increasing effect on ghrelin levels. Accordingly, it has been shown that a ghrelin rise occurs before or in the expectation of a meal and that lean subjects have higher ghrelin levels than obese ones (1,2,20). Furthermore, ghrelin is a potent vasodilator and has been shown to play a role in regulation of vascular tone (21).…”

“…Ghrelin seems to play a central role in GH regulation as well as in central energy balance, increasing appetite, food intake, and lipogenesis, hence promoting a positive energy balance (1,2). Ghrelin acts on GH release both via direct stimulation and via promoting GHRH stimulation (3,4).…”

The effect of interval versus continuous exercise on plasma leptin and ghrelin concentration in young trotters

“…This hormone increases appetite, food intake, energy balance and as a result, body weight (Hayashida et al 2001, Gil-Campos et al 2006. In cases of low-caloric diets or chronic exercise the plasma ghrelin level in horses increased (Gordon and McKeever 2005).…”

“…Ghrelin, which is produced mainly in the stomach, as well as in other gastrointestinal segments and selected areas of the brain, plays an opposite role (Gil-Campos et al 2006). This hormone increases appetite, food intake, energy balance and as a result, body weight (Hayashida et al 2001, Gil-Campos et al 2006.…”