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

被引:5
作者
Panajatovic, Miljenko V. [1 ,2 ]
Singh, Francois [1 ]
Krahenbuhl, Stephan [1 ]
Bouitbir, Jamal [3 ]
机构
[1] Univ Hosp Basel, Div Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland
[2] Univ Basel, Dept Pharmaceut Sci, Div Pharmaceut Technol, CH-4056 Basel, Switzerland
[3] Univ Basel, Dept Pharmaceut Sci, Div Mol & Syst Toxicol, CH-4056 Basel, Switzerland
关键词
simvastatin; PGC-1α fatty acids; triglycerides; lipid droplets; perilipin; 5; carnitine palmitoyltransferase 1b (CPT1b); SKELETAL-MUSCLE; GLUCOSE-HOMEOSTASIS; 000; PARTICIPANTS; LDL CHOLESTEROL; INDIVIDUAL DATA; STATIN THERAPY; METAANALYSIS; MECHANISM; INTOLERANCE; OXIDATION;
D O I
10.3390/ijms22094950
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-1 alpha overexpression (PGC-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha 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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页数:15
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