Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol

The lipid composition of cellular membranes is regulated to maintain membra ne fluidity. A key enzyme involved in this process is the membrane-bound st earoyl-CoA desaturase (SCD) which is the rate-limiting enzyme in the cellul ar synthesis of monounsaturated fatty acids from saturated fatty acids. A p roper ratio of saturated to monounsaturated fatty acids contributes to memb rane fluidity, Alterations in this ratio have been implicated in various di sease states including cardiovascular disease, obesity non-insulin-dependen t diabetes mellitus, hypertension, neurological diseases, immune disorders, and cancer. The regulation of stearoyl-CoA desaturase is therefore of cons iderable physiological importance and its activity is sensitive to dietary changes, hormonal imbalance, developmental processes, temperature changes, metals, alcohol, peroxisomal proliferators, and phenolic compounds. Two mou se and rat SCD genes (SCD1 and SCD2) and a single human SCD gene have been cloned and characterized, In the past several years we have studied the die tary influences on the genetic expression of the mouse stearoyl-CoA desatur ase. The expression of the mouse SCD genes is regulated by polyunsaturated fatty acids and cholesterol at the levels of transcription and mRNA stabili ty, Promoter elements that are responsible for the polyunsaturated fatty ac id repression colocalize with the promoter elements for SREBP-mediated regu lation of the SCD genes, It is the goal of this revi(e)w to provide an over view of the genetic regulation of the stearoyl-Coa desaturase in response t o dietary polyunsaturated fatty acids and cholesterol.