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 mu g 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.