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Publication : Effects of Simvastatin on Lipid Metabolism in Wild-Type Mice and Mice with Muscle PGC-1α Overexpression.

First Author  Panajatovic MV Year  2021
Journal  Int J Mol Sci Volume  22
Issue  9 PubMed ID  34066911
Mgi Jnum  J:312282 Mgi Id  MGI:6753537
Doi  10.3390/ijms22094950 Citation  Panajatovic MV, et al. (2021) Effects of Simvastatin on Lipid Metabolism in Wild-Type Mice and Mice with Muscle PGC-1alpha Overexpression. Int J Mol Sci 22(9)
abstractText  Previous studies suggest that statins may disturb skeletal muscle lipid metabolism potentially causing lipotoxicity with insulin resistance. We investigated this possibility in wild-type mice (WT) and mice with skeletal muscle PGC-1alpha overexpression (PGC-1alpha OE mice). In WT mice, simvastatin had only minor effects on skeletal muscle lipid metabolism but reduced glucose uptake, indicating impaired insulin sensitivity. Muscle PGC-1alpha overexpression caused lipid droplet accumulation in skeletal muscle with increased expression of the fatty acid transporter CD36, fatty acid binding protein 4, perilipin 5 and CPT1b but without significant impairment of muscle glucose uptake. Simvastatin further increased the lipid droplet accumulation in PGC-1alpha OE mice and stimulated muscle glucose uptake. In conclusion, the impaired muscle glucose uptake in WT mice treated with simvastatin cannot be explained by lipotoxicity. PGC-1alpha OE mice are protected from lipotoxicity of fatty acids and triglycerides by increased the expression of FABP4, formation of lipid droplets and increased expression of CPT1b.
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