Stearoyl-CoA desaturase 1 deficiency increases insulin signaling and glycogen accumulation in brown adipose tissue.
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 alpha-p85 subunit of phosphatidylinositol 3-kinase as well as Akt-Ser(473) and Akt-Thr(308) phosphorylation 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-(14)C]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.
Rahman
Shaikh Mizanoor
SM
Dept. of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
Dobrzyn
Agnieszka
A
Lee
Seong-Ho
SH
Dobrzyn
Pawel
P
Miyazaki
Makoto
M
Ntambi
James M
JM
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency*
D007328:Insulin; D006003:Glycogen; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D011972:Receptor, Insulin; D005947:Glucose