Central administration of leptin inhibits food intake and activates the sympathetic nervous system in rhesus macaques

The present study was performed to determine the effects of central adminis tration of leptin on food intake and sympathetic nervous system activity in a nonrodent species, the rhesus monkey. Peripheral administration of lepti n at doses (1 and 3 mu g/kg, sc) that produced increments of circulating le ptin concentrations within a physiological range did not inhibit food intak e over the subsequent 3 days. In contrast, leptin (l mu g/kg, intracerebrov entricularly) had no acute effect on food intake, but caused a significant and sustained suppression (40-50%) of food intake during the entire followi ng day (P < 0.01). In addition, circulating norepinephrine levels increased by 55 +/- 16% (P < 0.02) Ih after intracerebroventricular leptin administr ation, but did not increase after artificial cerebrospinal fluid administra tion. These results indicate that leptin can provide a signal to the centra l nervous system that decreases food intake in primates and in addition acu tely activates the sympathetic nervous system. However, the results showing an acute increase in circulating leptin concentrations after peripheral ad ministration of human leptin suggest that in primates, increases in circula ting leptin within the physiological range do not acutely regulate food int ake. Leptin may be more important in regulating food intake when there are sustained changes in circulating concentrations of leptin (e.g. with obesit y, prolonged energy restriction, or diabetes).