Recombinant Leptin Promotes Atherosclerosis and Thrombosis in Apolipoprotein E–Deficient Mice

Objective— The direct role of leptin in vascular disease remains controversial. The objective of this study was to examine the effects of leptin treatment on atherosclerosis and thrombosis in atherosclerotic-prone mice.Methods and Results— Sixteen-week-old, male apolipoprotein E–deficient mice were treated with injections of recombinant leptin (125 μg per day IP; n=10) or vehicle (n=10) for 4 weeks. Leptin treatment resulted in reduced epididymal fat (352±30.7 versus 621±61.5 mg;P =0.005) and fasting insulin (0.57±0.25 versus 1.7±0.22 ng/mL;P =0.014). Despite these metabolic benefits, leptin treatment resulted in an increase in atherosclerosis (8.0±0.95% versus 5.4±0.59% lesion surface coverage;P <0.05). Leptin treatment also resulted in a shortened time to occlusive thrombosis after vascular injury (21±2.1 versus 34.6±5.4 minutes;P =0.045).Conclusions— These studies indicate that exogenous leptin promotes atherosclerosis and thrombosis and support the concept that elevations of leptin may increase the risk for cardiovascular disease.