A LEPTIN DOSE-RESPONSE STUDY IN OBESE (OB OB) AND LEAN (+/) MICE/

This experiment determined the amount of leptin required to correct di fferent abnormalities in leptin-deficient ob/ob mice. Baseline food in takes and body weights of lean (+/?) and obese (ob/ob) C57B1/6J <ob> m ice were recorded for 7 days. An Alzet miniosmotic pump was placed in the peritoneal cavity of each mouse and delivered 0, 1, 2, 5, 10, or 4 2 mu g/day human leptin for 7 days. In ob/ob mice, 2 mu g leptin/day r educed food intake and body weight, and increased hypothalamic and bra in stem serotonin concentrations. All fat pads were reduced 35-40% by 10 mu g leptin/day, and liver weight, lipid, and glycogen decreased. S erum insulin and glucose were reduced in all leptin-treated ob/ob mice , and levels were normalized by 10 mu g/day leptin. Low rectal tempera tures of ob/ob mice were corrected by 10 and 42 mu g/day leptin. These doses also increased brown adipose tissue uncoupling protein expressi on. The only responses in lean mice were a transient reduction in food intake and weight loss with 10 or 42 mu g/day leptin. This study show s enhanced leptin sensitivity in ob/ob mice and suggests that increase d temperature and sympathetic activity are indirect responses to high concentrations of protein.