Stearoyl‐CoA desaturase‐3 mediates the regulation of adipose and hepatic murine lipid metabolism (605.1)

Abstract

Stearoyl‐CoA desaturase (SCD) is a critical enzyme involved in de novo lipogenesis and catalyzes the Δ9 desaturation of saturated fatty acids. Four SCD isoforms have been identified in mouse (SCD1‐4); SCD isoform 3 exhibits unique substrate specificity and tissue expression. 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, preputial glands and differentiating adipocytes. To determine the role of SCD3 in murine lipid metabolism, we created a mouse model in which SCD3 is globally knocked out. Despite the limited tissue expression of this isoform, SCD3‐/‐ mice exhibit a global phenotype when fed a lipogenic low‐fat high‐carbohydrate diet. In contrast to SCD1 deletion, which protects mice from diet‐induced obesity and hepatic steatosis, deletion of SCD3 deletion predisposes mice to increased hepatic triglyceride accumulation under high‐carbohydrate feeding compared to SCD3flox mice. Gene expression studies in white adipose tissue reveal that SCD3 deletion and high‐carbohydrate feeding cause a transcriptional remodeling of subcutaneous white adipose tissue. Expression of genes involved in de novo lipogenesis, fatty acid oxidation, and uncoupling are simultaneously increased in the subcutaneous depot of SCD3‐/‐ mice.Grant Funding Source: Supported by NIH National Research Service Award T32 GM07215.