Effects of leptin on adipose tissue lipoprotein lipase in the obese ob/ob mouse

Abstract

OBJECTIVE: To characterize the adaptations of lipid metabolism, with special emphasis on tissue lipoprotein lipase, to negative energy balance brought by chronic treatment of obese ob/ob mice with leptin.

DESIGN: According to a 2×2 factorial analysis, lean and obese C57BL/6J mice were subcutaneously infused with leptin (100 μg·kg⁻¹·day⁻¹) or vehicle (phosphate-buffered saline) during seven days.

RESULTS: Cumulative food intake and final body weight of vehicle-infused obese mice were twofold higher than in lean controls. Leptin decreased cumulative food intake and body weight of obese, but not lean mice. Lipoprotein lipase (LPL) activity in white inguinal and epididymal and brown interscapular adipose tissues of control obese mice was at least twofold higher than in lean mice, but comparable in the vastus lateralis muscle. Leptin treatment of obese mice significantly lowered LPL activity to that of lean mice in all tissues examined. Vehicle-infused obese mice had higher liver triglyceride content and were hypertriglyceridemic compared to lean mice, and triglyceride concentrations in plasma and liver were decreased proportionally after leptin treatment. Leptin lowered glycemia and insulinemia of obese mice to lean levels and decreased plasma corticosterone. Leptin infusion had no notable effect on tissue lipoprotein lipase nor plasma variables of lean mice.

CONCLUSIONS: Leptin infusion abolished hyperinsulinemia in the ob/ob mouse, an effect that was probably responsible for the concomitant normalization of adipose LPL activity. This study shows that decreased LPL activity, plasma triglyceride concentrations and hepatic triglyceride production constitute some of the adaptive peripheral adaptations of lipid metabolism, which accompany the reduction in fat mass accretion brought by leptin treatment of the obese ob/ob mouse.