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 -MSK (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. (C) 2001 Elsevier Science B.V. All rights reserved.