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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.
Highlights
Stearoyl-CoA desaturase (SCD)1 converts saturated fatty acids into monounsaturated fatty acids
We are uncertain as to why this muscle tissue was increased to such an extent; it is possible that its uniform composition or the fact that it is a highly active muscle tissue even in sedentary mice could cause stearoyl-CoA desaturase-1 (SCD1) mRNA overexpression to persist at greater levels compared with other muscle tissues
In KO models, there is a clear and consistent prevention of diet-induced obesity [12, 13, 17, 43,44,45], yet investigators could not explain these results in light of the fact that insulin sensitivity was increased with a concomitant impairment in TG and/or monounsaturated fatty acids (MUFA) synthesis
Summary
Stearoyl-CoA desaturase (SCD) converts saturated fatty acids into monounsaturated fatty acids. We sought to determine the role of SCD1 expression in glucose and lipid metabolism and its effects on exercise capacity in mice. 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 PPAR␦ expression and activity. SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPAR␦ expression in mice. The current study was intended to define the role of a key lipogenic enzyme, stearoyl-CoA desaturase-1 (SCD1), in regulating skeletal muscle lipid metabolism and how its overexpression can promote fat oxidation, exercise capacity, and glucose tolerance by increasing triglyceride synthesis.
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