A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis

Abstract

Stearoyl-CoA desaturase (SCD) catalyzes the de novo biosynthesis of oleate and palmitoleate, which are the major fatty acids found in triglycerides, cholesteryl esters, and phospholipids. A high carbohydrate (lipogenic) diet induces lipogenic gene expression by sterol regulatory element binding protein 1 (SREBP-1c)-mediated gene transcription, leading to an increase in the synthesis of triglycerides. The lipogenic diet fed to mice with a null mutation in the SCD1 gene (SCD −/−) fails to induce the synthesis of triglycerides in liver, despite the induction of expression of SREBP-1 and its target genes, fatty acid synthase and glycerol-3-phosphate acyltransferase. The lipogenic diet led to a decrease in the levels of triglyceride, but an increase in the level of cholesteryl esters of saturated fatty acids. Feeding a lipogenic diet supplemented with high levels of oleate to the SCD −/− mice resulted in incorporation of oleate in the liver of SCD −/− mice, but failed to restore triglycerides to the levels in the normal mouse.Triglyceride synthesis, as measured by the incorporation of [3H]glycerol, was dramatically reduced in the liver of SCD −/− mouse fed a lipogenic diet compared with the normal mouse. These observations demonstrate that induction of triglyceride synthesis is highly dependent on SCD1 gene expression.—Miyazaki, M., Y-C. Kim, and J. M. Ntambi. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J. Lipid Res. 2001. 42: 1018–1024.

Keywords

• triglycerides
• cholesteryl esters
• gene expression
• SREBP