Forbes S, Bui S, Robinson B R, Hochgeschwender U, Brennan M B
Eleanor Roosevelt Institute for Cancer Research, 1899 Gaylord Street, Denver, CO 80206, USA.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4233-7. doi: 10.1073/pnas.071054298. Epub 2001 Mar 20.
Leptin deficiency results in a complex obesity phenotype comprising both hyperphagia and lowered metabolism. The hyperphagia results, at least in part, from the absence of induction by leptin of melanocyte stimulating hormone (MSH) secretion in the hypothalamus; the MSH normally then binds to melanocortin-4 receptor expressing neurons and inhibits food intake. The basis for the reduced metabolic rate has been unknown. Here we show that leptin administered to leptin-deficient (ob/ob) mice results in a large increase in peripheral MSH levels; further, peripheral administration of an MSH analogue results in a reversal of their abnormally low metabolic rate, in an acceleration of weight loss during a fast, in partial restoration of thermoregulation in a cold challenge, and in inducing serum free fatty acid levels. These results support an important peripheral role for MSH in the integration of metabolism with appetite in response to perceived fat stores indicated by leptin levels.
瘦素缺乏会导致一种复杂的肥胖表型，包括食欲亢进和新陈代谢减缓。食欲亢进至少部分是由于下丘脑缺乏瘦素诱导的促黑素细胞激素（MSH）分泌；正常情况下，MSH会与表达黑皮质素-4受体的神经元结合并抑制食物摄入。代谢率降低的原因一直不明。在此我们表明，给瘦素缺乏（ob/ob）小鼠注射瘦素会导致外周MSH水平大幅升高；此外，外周注射MSH类似物会使其异常低的代谢率逆转，在禁食期间加速体重减轻，在冷刺激中部分恢复体温调节，并诱导血清游离脂肪酸水平。这些结果支持了MSH在响应瘦素水平所指示的感知脂肪储存时，在将新陈代谢与食欲整合方面的重要外周作用。
