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Appetite is regulated by a complex system of central and peripheral signals that interact in order to modulate eating behavior according the individual needs, i.e. the fasting or fed condition and the general nutritional status. Peripheral regulation includes adiposity signals and satiety signals, while central control is accomplished by several effectors, including the neuropeptidergic, monoaminergic and endocannabinoid systems. Adiposity signals inform the brain of the general nutritional status of the subject as indicated by the extent of fat depots. Indeed, leptin produced by the adipose tissue and insulin, whose pancreatic secretion tends to increase with the increase of fat mass, convey to the brain an anorexigenic message. Satiety signals, including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), originate from the gastrointestinal tract during a meal and, through the vagus nerve, reach the nucleus tractus solitarius (NTS) in the caudal brainstem. From NTS afferents fibers project to the arcuate nucleus (ARC) of the hypothalamus, where satiety signals are integrated with adiposity signals and with several hypothalamic and supra-hypothalamic inputs, thus creating a complex network of neural circuits that finally elaborate the most appropriate response, in terms of eating behavior. In more detail, ARC neurons secrete a number of neuropeptides with orexigenic properties, such as neuropeptide Y (NPY) and agouti-related peptide (AGRP), or anorexigenic effects such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Other brain areas involved in the control of food intake are located downstream the ARC: among these, the paraventricular nucleus (PVN), which produces anorexigenic peptides such as thyrotropin releasing hormone (TRH), corticotrophin releasing hormone (CRH) and oxytocin, the lateral hypothalamus (LHA) and perifornical area (PFA), secreting the orexigenic substances orexin-A (OXA) and melanin concentrating hormone (MCH). Recently, a great interest has developed for endogenous cannabinoids, important players in the regulation of food intake and energy metabolism. In the same context, increasing evidence is accumulating for a role played by the microbiota, the trillion of microorganism populating the human gastrointestinal tract.
The complex interaction between the peripheral organs and the central nervous system has generated the concept of gut-brain axis, now incorporated into the physiology. A better understanding of the mechanisms governing the eating behavior will allow the development of drugs capable of reducing or enhancing food consumption.