Hagan M M, Rushing P A, Schwartz M W, Yagaloff K A, Burn P, Woods S C, Seeley R J
Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0559, USA.
J Neurosci. 1999 Mar 15;19(6):2362-7. doi: 10.1523/JNEUROSCI.19-06-02362.1999.
The voluntary suppression of food intake that accompanies involuntary overfeeding is an effective regulatory response to positive energy balance. Because the pro-opiomelanocortin (POMC)-derived melanocortin system in the hypothalamus promotes anorexia and weight loss and is an important mediator of energy regulation, we hypothesized that it may contribute to the hypophagic response to overfeeding. Two groups of rats were overfed to 105 and 116% of control body weight via a gastric catheter. In the first group, in situ hybridization was used to measure POMC gene expression in the rostral arcuate (ARC). Overfeeding increased POMC mRNA in the ARC by 180% relative to levels in control rats. For rats in the second group, the overfeeding was stopped, and they were infused intracerebroventricularly with SHU9119 (SHU), a melanocortin (MC) antagonist at the MC3 and MC4 receptor, or vehicle. Although SHU (0.1 nmol) had no effect on food intake of control rats, intake of overfed rats increased by 265% relative to CSF-treated controls. This complete reversal of regulatory hypophagia not only maintained but actually increased the already elevated weight of overfed rats, whereas CSF-treated overfed rats lost weight. These results indicate that CNS MCs mediate hypophagic signaling in response to involuntary overfeeding and support the hypothesis that MCs are important in the central control of energy homeostasis.
伴随非自愿性过度喂养出现的食物摄入量的自主抑制是对正能量平衡的一种有效调节反应。由于下丘脑中源自阿片-促黑素细胞皮质素原（POMC）的促黑素细胞皮质素系统会促进厌食和体重减轻，并且是能量调节的重要介质，我们推测它可能有助于对过度喂养产生的摄食减少反应。通过胃导管将两组大鼠的进食量增加至对照体重的105%和116%。在第一组中，采用原位杂交法测量嘴侧弓状核（ARC）中的POMC基因表达。相对于对照大鼠的水平，过度喂养使ARC中的POMC mRNA增加了180%。对于第二组大鼠，停止过度喂养后，给它们脑室内注射SHU9119（SHU），这是一种作用于MC3和MC4受体的促黑素细胞皮质素（MC）拮抗剂，或注射赋形剂。虽然SHU（0.1 nmol）对对照大鼠的食物摄入量没有影响，但与注射脑脊液的对照大鼠相比，过度喂养大鼠的摄入量增加了265%。这种调节性摄食减少的完全逆转不仅维持了过度喂养大鼠已经升高的体重，实际上还使其体重增加，而注射脑脊液处理的过度喂养大鼠体重减轻。这些结果表明，中枢神经系统中的MCs介导了对非自愿性过度喂养的摄食减少信号传导，并支持了MCs在能量稳态的中枢控制中很重要这一假说。
