DIFFERENT CENTRAL AND PERIPHERAL RESPONSES TO LEPTIN IN RHESUS-MONKEYS - BRAIN TRANSPORT MAY BE LIMITED

The purpose of this experiment was to determine the effect of leptin a dministration on food intake and energy expenditure in rhesus monkeys. Four adult male rhesus monkeys, cannulated in the left lateral cerebr al ventricle, were used for all phases of this experiment. Food intake was measured following intracerebroventricular injections of vehicle or three doses (500 ng, 2 mu g, and 22 mu g) leptin. Leptin administra tion resulted in a dose-dependent decrease in food intake (P < 0.05), with food intake decreased by an average of 54% at 22 mu g leptin. Ene rgy expenditure was also measured at two intracerebroventricular doses of leptin. Energy expenditure was not different (P > 0.10) between pl acebo and leptin injections at either dose. Food intake was also measu red following iv injection of 3 mg leptin. In this case, leptin did no t alter (P > 0.10) food intake, despite increasing serum leptin levels by as much as 100-fold. These results suggest that leptin is a potent inhibitor of food intake in rhesus monkeys, but this effect requires elevation of leptin concentrations in the cerebrospinal fluid or criti cal brain sites. The transport system for movement of leptin across th e blood-brain barrier may limit the influence of circulating leptin on food intake in monkeys.