Stearoyl-CoA Desaturase-1 in the Regulation of Toll-Like Receptor Signaling and Endoplasmic Reticulum Stress Signaling

Abstract

Stearoyl-CoA desaturases are a family of enzymes that play a crucial role in the endogenous synthesis of monounsaturated fatty acids, also known as de novo lipogenesis. Of the four known SCD isoforms, stearoyl-CoA desaturase 1 (SCD1) is the most predominant and most ubiquitously expressed, with the highest induction in lipogenic tissues such as liver and adipose tissue. In this chapter, we will discuss the effects of SCD1 and its substrates, saturated fatty acids, on three levels as shown in Fig. 7.4. First, we will introduce SCD1 and its role in lipid biosynthesis. Next, we will cover intermediate responses to SCD1 modulation, such as inflammation and ER stress. Finally, we will expand our discussion of SCD1 into the context of vascular diseases such as atherosclerosis and vascular calcification. The studies discussed in this chapter are significant because cardiovascular diseases are some of the leading causes of mortality worldwide. In these diseases, lipids such as fatty acids and their metabolites can accumulate and lead to cellular dysfunction and death, known as lipotoxicity. Since SCD1 plays such an important role in fatty acid formation, a deeper understanding of this pivotal enzyme may significantly contribute to further advances in the treatment of lipid-related diseases.