Enhanced inhibitory feeding response to alpha-melanocyte stimulating hormone in the diet-induced obese rat.
A dysregulation in the hypothalamic neuropeptide systems involved in the control of appetite has previously been shown in models of diet-induced obesity. In the present study, male Sprague-Dawley rats were rendered obese by a highly palatable cafeteria-style diet over 20 weeks, while control rats had access to standard laboratory chow. Feeding responses to alpha-melanocyte stimulating hormone (alpha-MSH), an anorectic peptide and neuropeptide Y (NPY), a potent orexigenic agent were investigated in diet-induced obese and control animals. In addition, endogenous hypothalamic peptide levels were determined in these animals. Intracerebroventricular injections of either 4 nmol alpha-MSH or saline vehicle were given 10 min prior to the onset of the dark phase. Diet-induced obese rats had significantly enhanced nocturnal inhibitory feeding responses to alpha-MSH (P<0.05). The orexigenic feeding response induced by 1 nmol NPY was similar for both groups. At sacrifice, both alpha-MSH and NPY peptide content were selectively reduced in the paraventricular nucleus (PVN) of these animals (P<0.05). Although diet-induced obesity had no effect on responses to NPY, the significantly greater inhibition of nocturnal feeding by alpha-MSH and reduction in PVN alpha-MSH peptide level, suggests melanocortinergic signalling may be reduced in obesity which may account for the hyperphagia of these animals when presented with a palatable diet.
Hansen
M J
MJ
Department of Pharmacology, The University of Melbourne, Melbourne, 3010 Victoria, Australia.
Ball
M J
MJ
Morris
M J
MJ
D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D001835:Body Weight; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm; D004032:Diet; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000502:physiology / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain; D000521:alpha-MSH / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*
D009478:Neuropeptide Y; D000521:alpha-MSH