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 …