Regulation of stearoyl-CoA desaturase genes: Role in cellular metabolism and preadipocyte differentiation

The degree of fatty acid unsaturation in cell membrane lipids determines me mbrane fluidity, whose alteration has been implicated in a variety of disea se states including diabetes, obesity, hypertension, cancer, and neurologic al and heart diseases. Stearoyl-CoA desaturase (SCD) is a key rate-limiting enzyme in the synthesis of unsaturated fatty acids by insertion of a cis-d ouble bond in the Delta 9 position of fatty acid substrates. Palmitate and stearate are the preferred substrates, which are converted to palmitoleate and oleate, respectively. These monounsaturated fatty acids are the major c onstituents of cellular membrane phospholipids and triacylglycerol stores f ound in adipose tissue. Two mouse and rat SCD genes (SCD1 and SCD2) have be en cloned and characterized. During the differentiation of 3T3-L1 preadipoc ytes into adipocytes, SCD1 and SCD2 mRNAs are induced concomitant with incr eased de novo synthesis of palmitoleate and oleate. The physiological signi ficance of expressing the two isoforms in the adipocytes is currently unkno wn. In this review we discuss the role of the SCD isoforms in metabolism an d the recent findings on the differential regulation of mouse SCD genes by the antidiabetic thiazolidinediones (TZDs), during preadipocyte differentia tion. (C) 1999 Academic Press.