TY - JOUR T1 - Role of the CNS Melanocortin System in the Response to Overfeeding JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2362 LP - 2367 DO - 10.1523/JNEUROSCI.19-06-02362.1999 VL - 19 IS - 6 AU - Mary M. Hagan AU - Paul A. Rushing AU - Michael W. Schwartz AU - Keith A. Yagaloff AU - Paul Burn AU - Stephen C. Woods AU - Randy J. Seeley Y1 - 1999/03/15 UR - http://www.jneurosci.org/content/19/6/2362.abstract N2 - 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 situhybridization 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. ER -