Effects of Simvastatin on Lipid Metabolism in Wild-Type Mice and Mice with Muscle PGC-1α Overexpression |
| |
| Authors: | Miljenko V Panajatovic Francois Singh Stephan Krhenbühl Jamal Bouitbir |
| |
| Affiliation: | 1.Division of Clinical Pharmacology & Toxicology, University Hospital of Basel, CH-4031 Basel, Switzerland; (M.V.P.); (F.S.); (S.K.);2.Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, CH-4056 Basel, Switzerland;3.Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, CH-4056 Basel, Switzerland |
| |
| 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. |
| |
| Keywords: | simvastatin PGC-1α fatty acids triglycerides lipid droplets perilipin 5 carnitine palmitoyltransferase 1b (CPT1b) |
|
|
