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- Title
Effects of Simvastatin on Lipid Metabolism in Wild-Type Mice and Mice with Muscle PGC-1α Overexpression.
- Authors
Panajatovic, Miljenko V.; Singh, Francois; Krähenbühl, Stephan; Bouitbir, Jamal; Villani, Gaetano
- Abstract
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-1α overexpression (PGC-1α 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-1α 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-1α 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-1α 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.
- Subjects
LIPID metabolism; SIMVASTATIN; INSULIN sensitivity; MUSCLE metabolism; MICE; SKELETAL muscle
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 9, p4950
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22094950