Regulation of Rat Hepatic Elongase and Desaturase Expression

Abstract

Hepatic fatty acid elongases (Elovl-1, -2, -5 & -6) and desaturases [delta-5 (D5D), delta-6 (D6D), delta-9 (D9D)] play an important role in hepatic and whole body lipid composition. In contrast to the desaturases, little is known about the control of elongase expression. We examined the role insulin, glucose, sterol regulatory element binding protein (SREBP-1) and liver X receptors (LXR) play in the control of these enzymes in rat primary hepatocytes. Insulin induction of Elovl-6 and D5D, D6D and D9D mRNA correlated with elevated hepatocyte SREBP-1 nuclear content. In the absence of insulin, overexpressed mature SREBP-1c induced Elovl-6, D5D and D6D, but not D9D mRNA. The LXR agonist, T0-901317, induced all 3 desaturases, but no elongase. Glucose induction of Elovl-6 and D9D mRNA correlated with increased carbohydrate regulatory element binding protein (ChREBP) nuclear abundance. Over expression of dominant negative Max-like factor X (MLX) attenuated the glucose induction of these enzymes, implicating the ChREBP/MLX heterodimer in the glucose/insulin control of Elovl-6 and D9D expression. In conclusion, SREBP-1, ChREBP/MLX and LXR control hepatic lipid composition, at least in part, by regulating hepatic fatty acid elongase and desaturase expression. Supported by NIH DK43220, USDA 2003-5200-3400 and MAES.