Chronic effects of intracerebral ventricular enterostatin in Osborne-Mendel rats fed a high-fat diet.

Enterostatin, a pentapeptide found in the procolipase molecule of the pancreas, has been infused chronically into the lateral ventricle of Osborne-Mendel rats for 11 days. Treatment with enterostatin acutely lowered food intake more in the treated animals than in the vehicle-treated controls. Weight gain and serum insulin were significantly reduced by enterostatin. Corticosterone was significantly increased in rats receiving chronic infusions of enterostatin into the lateral ventricle and was also increased following an acute ICV injection of enterostatin. CRH antagonist did not block the acute feeding response to enterostatin in Sprague-Dawley rats. The elevation of corticosterone during chronic infusion of enterostatin reduced the level of hepatic glucocorticoid receptor as measured by Western blot. We conclude that body weight gain of OM rats is reduced by centrally administered enterostatin, and that the acute effects of enterostatin on food intake are not mediated through stimulation of CRH secretion.