Hypothalamic regulation of body growth and appetite by ghrelin-derived peptides during balanced nutrition or undernutrition

- Preproghrelin encodes several peptides with antagonistic actions on hypothalamic neuronal circuits that control appetite and GH secretion.
- Heterodimerization of GHS-R with other G-protein coupled receptors is a novel mechanism of regulation of the ghrelin pathways.
- Modulation of ghrelin-derived peptides in anorexia nervosa may be an adaptative metabolic response to undernutrition.

Among the gastrointestinal hormones that regulate food intake and energy homeostasis, ghrelin plays a unique role as the first one identified to increases appetite and stimulate GH secretion. This review highlights the latest mechanism by which ghrelin modulates body growth, appetite and energy metabolism by exploring pharmacological actions of the hormone and consequences of genetic or pharmacological blockade of the ghrelin/GHS-R (Growth Hormone Secretagogue Receptor) system on physiological responses in specific nutritional situations. Within the hypothalamus, novel mechanisms of action of this hormone involve its interaction with other ghrelin-derived peptides, such as desacyl ghrelin and obestatin, which are thought to act as functional ghrelin antagonists, and possible modulation of the GHS-R with other G-protein coupled receptors. During chronic undernutrition such as anorexia nervosa, variations of ghrelin-derived peptides may be an adaptative metabolic response to maintain normal glycemic control. Interestingly, some of ghrelin's metabolic actions are thought to be relayed through modulation of GH, an anabolic and hyperglycemic agent.