Neuroendocrine control of food intake.
Appetite is regulated by a complex system of central and peripheral signals which interact in order to modulate the individual response to nutrient ingestion. Peripheral regulation includes satiety signals and adiposity signals, while central control is accomplished by several effectors, including the neuropeptidergic, monoaminergic and endocannabinoid systems. Satiety signals, including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), originate from the gastrointestinal (GI) 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), where satiety signals are integrated with adiposity signals, namely leptin and insulin, and with several hypothalamic and supra-hypothalamic inputs, thus creating a complex network of neural circuits which finally elaborate the individual response to a meal. As for the neuropeptidergic system, ARC neurons secrete orexigenic substances, such as neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic peptides 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). A great interest in endocannabinoids, important players in the regulation of food intake, has recently developed. In conclusion, the present work reviews the most recent insights into the complex and redundant molecular mechanisms regulating food intake, focusing on the most encouraging perspectives for the treatment of obesity.
Chair of Endocrinology, University of Milan, Ospedale San Luca IRCCS, Istituto Auxologico Italiano, Via Spagnoletto 3, 20149 Milan, Italy.
Elena
E
Valassi
Massimo
M
Scacchi
Francesco
F
Cavagnini
D050154:Adiposity; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D001069:Appetite Regulation / Q000187:drug effects; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism; D005247:Feeding Behavior; D054439:Ghrelin / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D019894:Peptide YY / Q000378:metabolism; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism; D012528:Satiety Response; D015398:Signal Transduction / Q000187:drug effects
D019440:Anti-Obesity Agents; D015306:Biogenic Monoamines; D063385:Cannabinoid Receptor Modulators; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D009479:Neuropeptides; D010906:Pituitary Hormone-Releasing Hormones; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin