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Publication : SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARĪ“ expression in mice.

First Author  Rogowski MP Year  2013
Journal  J Lipid Res Volume  54
Issue  10 Pages  2636-46
PubMed ID  23918045 Mgi Jnum  J:202621
Mgi Id  MGI:5520125 Doi  10.1194/jlr.M035865
Citation  Rogowski MP, et al. (2013) SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARdelta expression in mice. J Lipid Res 54(10):2636-46
abstractText  Stearoyl-CoA desaturase (SCD)1 converts saturated fatty acids into monounsaturated fatty acids. Using muscle overexpression, we sought to determine the role of SCD1 expression in glucose and lipid metabolism and its effects on exercise capacity in mice. Wild-type C57Bl/6 (WT) and SCD1 muscle transgenic (SCD1-Tg) mice were generated, and expression of the SCD1 transgene was restricted to skeletal muscle. SCD1 overexpression was associated with increased triglyceride (TG) content. The fatty acid composition of the muscle revealed a significant increase in polyunsaturated fatty acid (PUFA) content of TG, including linoleate (18:2n6). Untrained SCD1-Tg mice also displayed significantly increased treadmill exercise capacity (WT = 6.6 +/- 3 min, Tg = 71.9 +/- 9.5 min; P = 0.0009). SCD1-Tg mice had decreased fasting plasma glucose, glucose transporter (GLUT)1 mRNA, fatty acid oxidation, mitochondrial content, and increased peroxisome proliferator-activated receptor (PPAR)delta and Pgc-1 protein expression in skeletal muscle. In vitro studies in C2C12 myocytes revealed that linoleate (18:2n6) and not oleate (18:1n9) caused a 3-fold increase in PPARdelta and a 9-fold increase in CPT-1b with a subsequent increase in fat oxidation. The present model suggests that increasing delta-9 desaturase activity of muscle increases metabolic function, exercise capacity, and lipid oxidation likely through increased PUFA content, which increases PPARdelta expression and activity. However, the mechanism of action that results in increased PUFA content of SCD1-Tg mice remains to be elucidated.
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