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, 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 [(3)H]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
M
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
Kim
Y C
YC
Ntambi
J M
JM
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D005796:Genes / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides / Q000096:biosynthesis* / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; D002788:Cholesterol Esters; D004268:DNA-Binding Proteins; D004040:Dietary Carbohydrates; D005229:Fatty Acids, Monounsaturated; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; D013230:Stearoyl-CoA Desaturase