The Concept of CMR

Neuropeptides and appetite regulation

The purpose of this section on neuropeptides and food intake is to introduce the role of neuropeptides from the periphery and central nervous system in regulating appetite. It is not designed to provide exhaustive information on central regulation of human appetite.

The hypothalamus is frequently referred to as the “feeding” or “satiety” centre. The main regions of the hypothalamus involved in energy intake are the arcuate and the paraventricular nucleus. Both regions secrete orexigenic and anorexigenic peptides.

The main role of orexigenic neuropeptides is to restore body fat stores (i.e., restore energy balance) when energy deficits occur. Neuropeptide Y (NPY) is one of the most abundant orexigenic peptides. It is mostly secreted by neurons of the arcuate nucleus and reaches other hypothalamic targets, such as the paraventricular nucleus and the dorsomedial hypothalamic nucleus, prior to feeding (4). NPY is present at very high concentrations during starvation, but overeating does not raise hypothalamic NPY levels (5). Similar to NPY, melanin-concentrating hormone (MCH), a peptide produced in the lateral hypothalamus, uses G-coupled receptors to modulate food intake. MCH receptors are found in the hippocampus, amygdala, and cerebral cortex. Though the role of MCH is not fully understood, it has been shown in rats that acute intracerebrovascular injections of MCH can induce intake of high-calorie, energy-dense food, suggesting that it plays a role in energy balance (6). Ghrelin is an orexigenic peptide produced by the gut, mostly by the cells of the human gastric mucosa. Circulating ghrelin levels are particularly high before feeding and are acutely downregulated by refeeding (7).