Leptin upregulates caveolin-1 expression: Implications for development of atherosclerosis

Abstract 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 caveo...

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Bibliographic Details
Published in:Atherosclerosis 2011-08, Vol.217 (2), p.499-502
Main Authors: Singh, Prachi, Peterson, Timothy E, Sert-Kuniyoshi, Fatima H, Jensen, Michael D, Somers, Virend K
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Atherosclerosis - etiology
Atherosclerosis - metabolism
Biological and medical sciences
Blood and lymphatic vessels
Blotting, Western
Cardiology. Vascular system
Cardiovascular
Caveolin 1 - genetics
Caveolin 1 - metabolism
Caveolin-1
Cell signaling
Cells, Cultured
endothelial cells
Endothelial Cells - metabolism
endothelial nitric oxide synthase
endothelium
Genetic Vectors
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Leptin
Leptin - metabolism
Medical sciences
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Nitric Oxide Synthase Type III - metabolism
Obesity
Orthopedic surgery
protein synthesis
Signal Transduction
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Time Factors
Transfection
Up-Regulation
Western blotting
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Summary:Abstract 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.
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2010.10.012