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

Stearoyl-CoA desaturase (SCD) catalyzes the de novo biosynthesis of oleate and palmitoleate, which are the major fatty acids found in triglycerides, c holesteryl esters, and phospholipids, A high carbohydrate (lipogenic) diet induces lipogenic gene expression by sterol regulatory element binding prot ein 1 (SREBP-1c)-mediated gene transcription, leading to an increase in the synthesis of triglycerides. The lipogenic diet fed to mice with a null mut ation in the SCD1 gene (SCD-/-) fails to induce the synthesis of triglyceri des in liver, despite the induction of expression of SREBP-1 and its target genes, fatty acid synthase and glycerol-3-phosphate acyltransferase, The l ipogenic diet led to a decrease in the levels of triglyceride, but an incre ase in the level of cholesteryl esters of saturated fatty acids. Feeding a lipogenic diet supplemented with high levels of oleate to the SCD-/- mice r esulted in incorporation of oleate in the liver of SCD-/- mice, but failed to restore triglycerides to the levels in the normal mouse. Triglyceride sy nthesis, as measured by the incorporation of [H-3]glycerol, was dramaticall y reduced in the Liver of SCD-/- mouse fed a lipogenic diet compared with t he normal mouse.jlr These observations demonstrate that induction of trigly ceride synthesis is highly dependent on SCD1 gene expression.