Peptides and proteins regulating food intake: a comparative view

Abstract

AbstractEnergy homeostasis is under multiple endocrine and neural controls that involve both central and peripheral hormones and neuropeptides. Disorders of energy balance (e.g., obesitas and anorexia nervosa) are caused by subtle dysregulation of these regulatory mechanisms. The hypothalamic arcuate nucleus is a main site of central regulation where two distinct subpopulations of neurons co-express either neuropeptide Y (NPY) and agouti-related protein (AgRP), or proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART): the former set of peptides increases food intake; the latter decreases food intake and affect energy metabolism. Key peripheral hormones affecting energy metabolism include cholecystokinin (CCK), leptin and insulin, which decrease food intake, and ghrelin, which increases food intake. CCK and ghrelin regulate food intake in the short term (by affecting meal size), whereas leptin and insulin regulate food intake over longer periods spanning several meals. These signals and their physiology are reasonably well understood in mammals. On the other hand, knowledge on energy metabolism in earlier vertebrates is scant. Recently characterised central food intake regulatory mechanisms in fish suggest that they operate in a manner similar to their mammalian counterparts. Peripheral mechanisms have been poorly studied outside mammals. The recent identification of leptin in several fish species provides new insights and opportunities to enhance our understanding of the regulation of food intake. Comparative analysis of these peripheral mechanisms may shed new light on the function and evolution of the mechanisms controlling energy homeostasis. In this review, we summarise recent developments in understanding of mechanisms and signals that regulate energy balance in mammals, and compare these to what we now know about their orthologues in earlier vertebrates, with a particular focus on bony fishes.