Leptin suppresses food intake and body weight in corticosterone-replaced adrenalectomized rats

Intracerebroventricular (ICV) injections of leptin decrease food intake and body weight while increasing energy expenditure. Some of these effects are reportedly enhanced in bilaterally adrenalectomized (ADX) rats. The purpose of the present experiment was to establish the time course of the suppression in body weight and food intake after an ICV injection of leptin. We wanted to establish the effect of varying doses of corticosterone (CORT) on body weight and food intake suppression by using separate groups of ADX, ADX and corticosterone-treated and sham-operated Sprague-Dawley rats. All rats were implanted with cholesterol pellets that varied in CORT content. During the same surgical session, all rats were fitted with a cannula in the lateral ventricle. After recovering from surgery, each rat was administered a 5- micro g ICV injection of leptin. ADX rats that were treated with CORT replacement lost more (P < 0.05) weight and took longer (P < 0.05) to return to baseline body weight than sham-operated controls. Leptin injection decreased food consumption to a greater extent (P < 0.05) in the ADX groups treated with CORT than in the sham-operated controls. Plasma insulin increased in a dose-dependent manner in the ADX rats as a function of CORT replacement. The higher of the two CORT replacement doses used in this experiment restored circulating CORT to levels observed in sham-operated controls. Contrary to earlier reports, physiological doses of CORT appear to enhance leptin-induced weight loss.