A leptin infusion dose response study in lean and obese ob mice

This study examined the effects of chronic infusion of leptin in lean and obese mice. C57BL/6J ob 5 week old female mice had free access to chow and water and were divided into groups of 6 lean or 6 obese mice. A 7 day Alzet pump was placed intraperitoneally in each mouse, delivering 0, 1, 2, 5, 10 or 42 ug/day human recombinant leptin. All doses of leptin suppressed food intake and caused weight loss in obese mice, with maximal effect at 10 ug/day. 10 or 42 ug/day caused a transient reduction in lean food intake, had no effect on body weight but reduced body fat. Leptin did not effect rectal temperature of lean mice but 10 and 42 ug/day elevated ob/ob temperatures. After 7 days of infusion, 2 ug/day, or more, leptin reduced serum insulin of ob/ob mice, with no effect in lean mice. Brown adipose uncoupling protein (UCP) expression was lower in obese than lean 0 ug/day mice, but was not different with leptin infusion. 10 and 42 ug/day leptin increased obese UCP expression, the same doses that increased rectal temperature. All doses of leptin reduced liver lipid and glycogen in obese mice, but not to the levels found in lean mice. The leptin induced changes in food intake and serum insulin of obese mice are probably physiological responses whereas elevation of obese temperature and reduced fat in lean mice may be in response to a pharmacological dose of protein.