Mj. Hansen et al., Enhanced inhibitory feeding response to alpha-melanocyte stimulating hormone in the diet-induced obese rat, BRAIN RES, 892(1), 2001, pp. 130-137
A dysregulation in the hypothalamic neuropeptide systems involved in the co
ntrol of appetite has previously been shown in models of diet-induced obesi
ty. In the present study, male Sprague-Dawley rats were rendered obese by a
highly palatable cafeteria-style diet over 20 weeks, while control rats ha
d access to standard laboratory chow. Feeding responses to alpha -melanocyt
e stimulating hormone (alpha -MSH), an anorectic peptide and neuropeptide Y
(NPY), a potent orexigenic agent were investigated in diet-induced obese a
nd control animals. In addition, endogenous hypothalamic peptide levels wer
e determined in these animals. Intracerebroventricular injections of either
4 nmol alpha -MSH or saline vehicle were given 10 min prior to the onset o
f the dark phase. Diet-induced obese rats had significantly enhanced noctur
nal inhibitory feeding responses to alpha -MSK (P<0.05). The orexigenic fee
ding response induced by 1 nmol NPY was similar for both groups. At sacrifi
ce, both <alpha>-MSH and NPY peptide content were selectively reduced in th
e paraventricular nucleus (PVN) of these animals (P<0.05). Although diet-in
duced 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 present
ed with a palatable diet. (C) 2001 Elsevier Science B.V. All rights reserve
d.