EFFECTS OF LEPTIN ON ADIPOSE-TISSUE LIPOPROTEIN-LIPASE IN THE OBESE OB OB MOUSE/

OBJECTIVE: To characterize the adaptations of lipid metabolism, with s pecial emphasis on tissue lipoprotein lipase, to negative energy balan ce brought by chronic treatment of obese ob/ob mice with leptin. DESIG N: According to a 2x2 factorial analysis, lean and obese C57BL/6J mice were subcutaneously infused with leptin (100 mu g.kg(-1).day(-1)) or vehicle (phosphate-buffered saline) during seven days. RESULTS: Cumula tive food intake and final body weight of vehicle-infused obese mice w ere twofold higher than in lean controls. Leptin decreased cumulative food intake and body weight of obese, but not lean mice. Lipoprotein l ipase (LPL) activity in white inguinal and epididymal and brown inters capular adipose tissues of control obese mice was at least twofold hig her than in lean mice, but comparable in the vastus lateralis muscle. Leptin treatment of obese mice significantly lowered LPL activity to t hat of lean mice in all tissues examined. Vehicle-infused obese mice h ad higher liver triglyceride content and were hypertriglyceridemic com pared to lean mice, and triglyceride concentrations in plasma and live r were decreased proportionally after leptin treatment. Leptin lowered glycemia and insulinemia of obese mice to lean levels and decreased p lasma corticosterone. Leptin infusion had no notable effect on tissue lipoprotein lipase nor plasma variables of lean mice. CONCLUSIONS: Lep tin infusion abolished hyperinsulinemia in the ob/ob mouse, an effect that was probably responsible for the concomitant normalization of adi pose LPL activity. This study shows that decreased LPL activity, plasm a triglyceride concentrations and hepatic triglyceride production cons titute some of the adaptive peripheral adaptations of lipid metabolism , which accompany the reduction in fat mass accretion brought by lepti n treatment of the obese ob/ob mouse.