Activation of hepatic acetyl-CoA carboxylase by S-nitrosylation in response to diet.

Abstract

Nitric oxide (NO), produced primarily by nitric oxide synthase (NOS) enzymes, is known to influence energy metabolism by stimulating fat uptake and oxidation. The effects of NO on de novo lipogenesis, however, are less clear. Here we demonstrate that hepatic expression of eNOS is reduced following prolonged administration of a hypercaloric high-fat diet. This results in marked reduction in the amount of S-nitrosylation of liver proteins including notably Acetyl-CoA Carboxylase (ACC), the rate-limiting enzyme in de novo lipogenesis. We further show that ACC S-nitrosylation markedly increases enzymatic activity. Diminished eNOS expression and ACC S-nitrosylation may thus represent a physiological adaptation to caloric excess by constraining lipogenesis. Our findings demonstrate that S-nitrosylation of liver proteins is subject to dietary control and suggest that de novo lipogenesis is coupled to dietary and metabolic conditions through ACC S-nitrosylation.