Leptin upregulates caveolin-1 expression: implications for development of atherosclerosis.

OBJECTIVE: To determine the role of hyperleptinemia on caveolin-1 expression and leptin signaling. METHODS: Endothelial cells are critical to atherosclerosis development; therefore we investigated hyperleptinemia in cultured vascular endothelial cells. Dose-dependent effect of leptin on caveolin-1 expression was determined by Western blot analysis. Also, the consequence of increased caveolin-1 expression on leptin signaling was investigated by adenovirus mediated caveolin-1 overexpression. The effect of increased caveolin-1 expression on leptin-dependent activation of ERK1/2 and eNOS was determined by Western blot analysis. RESULTS: Leptin upregulates caveolin-1 protein expression in a dose dependent manner and increased caveolin-1 expression impairs leptin signaling. CONCLUSIONS: Leptin increases caveolin-1 protein expression which impairs leptin signaling in vascular endothelial cells. Our study identifies an additional leptin mediated proatherogenic mechanism and a novel caveolin-1 dependent leptin feedback mechanism which may have implications for development of peripheral leptin resistance in the endothelium.