Dietary and Insulin Regulation of the Stearoyl-CoA Desaturase Genes
James M. Ntambi.
Departments of Biochemistry and Nutritional Sciences, The University of Wisconsin-Madison, WI, USA
Stearoyl CoA desaturase genes encode key enzymes involved in the biosynthesis of monounsaturated fatty acids as well as the regulation of this process. The SCD genes are under dietary and hormonal control. The SCD1 mRNA expression is decreased in rat liver during starvation and diabetes and is rapidly induced to high levels upon refeeding high carbohydrate diets or upon insulin administration. Diets rich in saturated fatty acids or cholesterol also induce SCD1 gene expression in rat liver. On the other hand, dietary w-3 and w-6 polyunsaturated fatty acids (PUFAs) diminish the insulin- or carbohydrate-induced expression of the SCD1 gene. The repression of the SCD genes by PUFAs occurs at the levels of gene transcription and mRNA stability. We have localized the polyunsaturated fatty acid responsive element (PUFA-RE) in the promoter of the SCD1 and SCD2 genes and we further found that these promoter elements colocalize with the elements to which the sterol regulatory element binding protein (SREBP) binds suggesting that the SREBP may mediate both PUFA and cholesterol regulation of the SCD genes in liver. In mature adipocytes the SCD genes are repressed by both w-6 and w-3 fatty acids mainly at the levels of mRNA stability. However, during the differentiation of preadipocytes into adipocytes the expression of the SCD genes as well as other lipogenic genes is repressed specifically by PUFAs of the w-6 series through MAPK-mediated phosphorylation of the peroxisome-proliferator activated receptor gamma 2 (PPARg-2).