title: 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 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.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Singh
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Peterson
authors.forename: Fatima H
authors.initials: FH
authors.lastname: Sert-Kuniyoshi
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jensen
authors.forename: Virend K
authors.initials: VK
authors.lastname: Somers
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005822:Genetic Vectors; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D020738:Leptin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3