Stearoyl-CoA desaturase 1 deficiency increases insulin signaling and glycogen accumulation in brown adipose tissue

Abstract

Stearoyl-CoA desaturase (SCD) catalyzes the synthesis of oleate (C18:1) and palmitoleate (C16:1), which are the main monounsaturated fatty acids of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Previously, we showed that SCD1 deficiency elevates insulin-signaling components and downregulates protein-tyrosine phosphatase-1B (PTP-1B) in muscle, a major insulin-sensitive tissue. Here we found that, in brown adipose tissue (BAT), another insulin-sensitive tissue, the basal tyrosine phosphorylations of insulin receptor (IR) and IR substrates (IRS-1 and IRS-2) were upregulated in SCD1^−/−mice compared with wild-type mice. The association of IRS-1 and IRS-2 with the α-p85 subunit of phosphatidylinositol 3-kinase as well as Akt-Ser⁴⁷³and Akt-Thr³⁰⁸phosphorylation is also elevated in the SCD1^−/−mice. The mRNA expression, protein levels, and activity of PTP-1B implicated in the attenuation of the insulin signal are reduced in the SCD1^−/−mice. The content of GLUT4 in the plasma membrane increased 2.5-fold, and this was accompanied by a 6-fold increase in glucose uptake in BAT of SCD1^−/−mice. The increased glucose uptake was associated with higher glycogen synthase activity and glycogen accumulation. In the presence of insulin, [U-¹⁴C]glucose incorporation into glycogen was increased in BAT of SCD1^−/−mice. Taken together, these studies illustrate increased insulin signaling and increased glycogen metabolism in BAT of SCD1^−/−mice.