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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2011 January 28; 286(4): e99909.
PMCID: PMC3024810

The FAS-NOS Connection♦

De Novo Lipogenesis Maintains Vascular Homeostasis through Endothelial Nitric-oxide Synthase (eNOS) Palmitoylation

♦ See referenced article, J. Biol. Chem. 2011, 286, 2933–2945

Dysfunction in the endothelium, which regulates vascular function and controls tissue access from the circulation, is commonly associated with diabetes and a precursor of vascular damage. Endothelial dysfunction is largely brought about by defects in endothelial nitric-oxide synthase (eNOS) due to insulin resistance and increased fatty acid oxidation. In this Paper of the Week, Xiaochao Wei and colleagues examined how fatty acid metabolism, specifically de novo lipogenesis, and eNOS activity are linked in more detail. Using mice with endothelial inactivated FAS (FASTie mice), they found that fatty-acid synthase (FAS), which drives lipogenesis, was physically associated with eNOS and targets eNOS to the plasma membrane; they also found that FAS, whose major metabolic product is palmitate, was required for the palmitoylation of eNOS. FASTie mice displayed increases in vascular permeability, inflammatory markers, leukocyte migration, and susceptibility to endotoxin-induced death, all indicative of a proinflammatory state; the mice also displayed inhibited angiogenesis in response to injury. De novo lipogenesis might seem unimportant for endothelial cells that are continually bathed in circulating fatty acids, yet these findings suggest a novel relationship between FAS and eNOS that links nutritional status to vascular integrity and may be a key contributor to vascular problems seen in diabetes and related metabolic disorders.

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Administration of low doses of LPS (endotoxin) causes greater inflammation in the lungs of FASTie mice (evidenced by inflammatory cell migration to the alveolar spaces, arrows) compared to wild type.

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