Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation.
Obesity is increasing in severity and prevalence in the United States and represents a major public health issue. No effective pharmacologic treatment leading to sustained weight loss currently exists. The growing interest in the regulation of food intake stems from the current drug treatments for obesity, almost all of which interfere with the monoamine system. Our knowledge of potential interactions between the orexigenic and anorexigenic pathways is limited and fragmented, making the development of targeted drug therapy for obesity difficult. The present review of the interaction of neuropeptides and monoamines emphasizes the complexity of the central mechanisms that regulate feeding behavior. Two main systems are implicated in food intake regulation: neuropeptide Y (NPY) and pro-opiomelanocortin. alpha-Melanocyte-stimulating hormone is a tridecapeptide cleaved from pro-opiomelanocortin that acts to inhibit food intake. The predominant NPY orexigenic receptors are NPY-Y1 and NPY-Y5, and the two anorexigenic melanocortin receptors involved in hypothalamic food intake control are MC3-R and MC4-R. Both neuropeptides interact with monoamines in the hypothalamus to control physiologic states such as hunger, satiation, and satiety. Serotonin suppresses food intake and body weight, acting mainly through the serotonin 1B receptor. Dopamine regulates hunger and satiety by acting in specific hypothalamic areas, through the D1 and D2 receptors. Noradrenaline activation of alpha1- and beta2-adrenoceptors decreases food intake, and stimulation of the alpha2-adrenoceptor increases food intake. A better understanding of the detailed mechanisms underlying the pathogenesis of hyperphagia and hypophagia is needed to develop new therapeutic approaches to obesity.
Ramos
Eduardo J B
EJ
Surgical Metabolism and Nutrition Laboratory, Department of Surgery, University Hospital, Upstate Medical University, Syracuse, New York, USA.
Meguid
Michael M
MM
Campos
Antonio C L
AC
Coelho
Julio C U
JC
D015306:Biogenic Monoamines / Q000378:metabolism / Q000502:physiology*; D004435:Eating / Q000502:physiology; D002149:Energy Intake / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D009478:Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000453:epidemiology / Q000517:prevention & control*; D000521:alpha-MSH / Q000378:metabolism / Q000502:physiology*
D015306:Biogenic Monoamines; D009478:Neuropeptide Y; D000521:alpha-MSH