title: SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARδ expression in mice.
abstract: 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)δ 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 PPARδ 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 PPARδ expression and activity. However, the mechanism of action that results in increased PUFA content of SCD1-Tg mice remains to be elucidated.
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX; and.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rogowski
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Flowers
authors.forename: Alexis D
authors.initials: AD
authors.lastname: Stamatikos
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
authors.forename: Chad M
authors.initials: CM
authors.lastname: Paton
mesh_terms: D000818:Animals; D002460:Cell Line; D017079:Exercise Tolerance; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D047494:PPAR delta; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D005947:Glucose
keywords: linoleate; oleate; peroxisome proliferator-activated receptor; polyunsaturated fatty acid sparing; stearoyl-CoA desaturase
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