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.
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: Ana Gómez-Ruiz; Fermín I Milagro; Javier Campión; J Alfredo Martínez; Carlos de Miguel Journal: J Cell Physiol Date: 2010-10 Impact factor: 6.384
Authors: Stephan Goetze; Anne Bungenstock; Cornelia Czupalla; Friedrich Eilers; Philipp Stawowy; Ulrich Kintscher; Chantel Spencer-Hänsch; Kristof Graf; Bernd Nürnberg; Ronald E Law; Eckart Fleck; Michael Gräfe Journal: Hypertension Date: 2002-11 Impact factor: 10.190
Authors: Babak Razani; Terry P Combs; Xiao Bo Wang; Philippe G Frank; David S Park; Robert G Russell; Maomi Li; Baiyu Tang; Linda A Jelicks; Philipp E Scherer; Michael P Lisanti Journal: J Biol Chem Date: 2001-12-05 Impact factor: 5.157
Authors: Prachi Singh; Timothy E Peterson; Fatima H Sert-Kuniyoshi; Jason A Glenn; Diane E Davison; Abel Romero-Corral; Snigdha Pusalavidyasagar; Michael D Jensen; Virend K Somers Journal: Circ Res Date: 2012-06-22 Impact factor: 17.367
Authors: Jaume Padilla; Nathan T Jenkins; Victoria J Vieira-Potter; M Harold Laughlin Journal: Am J Physiol Regul Integr Comp Physiol Date: 2013-02-06 Impact factor: 3.619