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De Novo Lipogenesis Maintains Vascular Homeostasis through Endothelial Nitric-oxide Synthase (eNOS) Palmitoylation
Wei, Xiaochao; Schneider, Jochen; Shenouda, Sherene M. et al.
2011In Journal of Biological Chemistry, 286 (4), p. 2933-2945
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Abstract :
[en] Endothelial dysfunction leads to lethal vascular complications in diabetes and related metabolic disorders. Here, we demonstrate that de novo lipogenesis, an insulin-dependent process driven by the multifunctional enzyme fatty-acid synthase (FAS), maintains endothelial function by targeting endothelial nitric-oxide synthase (eNOS) to the plasma membrane. In mice with endothelial inactivation of FAS (FASTie mice), eNOS membrane content and activity were decreased. eNOS and FAS were physically associated; eNOS palmitoylation was decreased in FAS-deficient cells, and incorporation of labeled carbon into eNOS-associated palmitate was FAS-dependent. FASTie mice manifested a proinflammatory state reflected as increases in vascular permeability, endothelial inflammatory markers, leukocyte migration, and susceptibility to LPS-induced death that was reversed with an NO donor. FAS-deficient endothelial cells showed deficient migratory capacity, and angiogenesis was decreased in FASTie mice subjected to hindlimb ischemia. Insulin induced FAS in endothelial cells freshly isolated from humans, and eNOS palmitoylation was decreased in mice with insulin-deficient or insulin-resistant diabetes. Thus, disrupting eNOS bioavailability through impaired lipogenesis identifies a novel mechanism coordinating nutritional status and tissue repair that may contribute to diabetic vascular disease.
Disciplines :
Cardiovascular & respiratory systems
Endocrinology, metabolism & nutrition
Identifiers :
UNILU:UL-ARTICLE-2012-148
Author, co-author :
Wei, Xiaochao
Schneider, Jochen ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Shenouda, Sherene M.
Lee, Ada
Towler, Dwight A.
Chakravarthy, Manu V.
Vita, Joseph A.
Semenkovich, Clay F.
Language :
English
Title :
De Novo Lipogenesis Maintains Vascular Homeostasis through Endothelial Nitric-oxide Synthase (eNOS) Palmitoylation
Publication date :
2011
Journal title :
Journal of Biological Chemistry
ISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
286
Issue :
4
Pages :
2933-2945
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 29 April 2016

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