The role of stearoyl‐CoA desaturase‐3 in lipid metabolism

Abstract

Stearoyl‐CoA desaturase (SCD) is a rate‐limiting enzyme in de novo lipogenesis that catalyzes the synthesis of monounsaturated fatty acids from saturated fatty acids. Four SCD isoforms have been identified in mouse (SCD1–4); SCD isoform 3 exhibits unique tissue expression and substrate specificity. While SCD1, 2, and 4 convert palmitate and stearate to palmitoleate and oleate, respectively, SCD3 preferentially desaturates palmitate. SCD3 expression is restricted to skin, harderian glands, and preputial glands. Despite the limited tissue expression of this isoform, SCD3−/− mice exhibit a global phenotype when fed a lipogenic low‐fat high‐carbohydrate diet. While deletion of SCD1 protects mice from diet‐induced obesity and hepatic steatosis, SCD3 deletion predisposes mice to increased lipogenesis in white adipose tissue and hepatic triglyceride accumulation. Gene expression studies in the harderian gland reveal that deletion of SCD1 causes a dramatic decrease in Scd3, while deletion of SCD3 results in an increase in Scd1. We propose that the observed increase in lipogenesis upon the deletion of this lipogenic enzyme stems from a regulatory mechanism between SCD isoforms. Funded by NIH.