Effect of a fatty acid synthas intake and expression of hyp neuropeptides

The fatty acid synthase inhibitor, C75, acts centrally to reduce food EJ intake and body weight in mice. Here we report the effects of C75 M on the expression of key orexigenic [neuropeptide Y (NPY), agoutiL related protein (AgRP), and melanin-concentrating hormone] and wI anorexigenic [pro-opiomelanocortin (POMC) and cocaine-amphetn amine-related transcript (CART)] neuropeptide messages in the aI hypothalami of lean and obese (ob/ob) mice. In lean mice, C75 N rapidly and almost completely blocked food intake and prevented ti fasting-induced up-regulation of hypothalamic AgRP and NPY m mRNAs, as well as down-regulation of CART and POMC mRNAs. m Thus, in lean mice C75 seems to interrupt the fasting-induced fr signals that activate expression of NPY and AgRP and suppression sy of POMC and CART. In obese mice, C75 rapidly suppressed food y intake, reduced body weight, and normalized obesity-associated Li hyperglycemia and hyperinsulinemia. Like its effect in lean mice, C75 prevented the fasting-induced increase of hypothalamic NPY Cl and AgRP mRNAs in obese mice, but had no effect on the exprescl sion of POMC and CART mRNAs. The suppressive effect of C75 on h( food intake in lean mice seems to be mediated both by NPY/AgRP wI and POMC/CART neurons, whereas in obese mice the effect seems O to be mediated primarily by NPY/AgRP neurons. In both lean and cl obese mice, C75 markedly increased expression of melaninp] concentrating hormone and its receptor in the hypothalamus. G