Coenzyme Q10 Ameliorates the Reduction in GLUT4 Transporter Expression Induced by Simvastatin in 3T3-L1 Adipocytes

Abstract

Statins significantly reduce cardiovascular events in a broad population of patients with hyperlipidemia. However, a small, but significant risk of new-onset diabetes has been reported in patients treated with statins. The mechanism by which statins cause diabetes has not been elucidated and therefore preventive strategies have yet to be defined. Our goal was to study the differing effects of a lipophilic (simvastatin) statin, hydrophilic (pravastatin) statin, and ezetimibe on glucose transporter-4 (GLUT4) protein expression in 3T3-L1 adipocytes. We hypothesized that the reductions in GLUT4 protein secondary to statin treatment would be prevented when cells were co-incubated with coenzyme Q10 (CoQ10). GLUT4 protein expression was determined using the In-Cell Western technique. Confluent adipocytes were differentiated using a hormonal cocktail for 3 days; followed by treatment with simvastatin, pravastatin, ezetimibe and CoQ10. Cell morphology was observed after treatment using phase-contrast microscopy. Treatment with simvastatin (P<0.001) and simvastatin plus ezetimibe (P<0.001) significantly decreased GLUT4 protein expression in the adipocytes compared to control conditions. GLUT4 protein levels were similar to control after treatment with ezetimibe alone (P=0.52) or pravastatin (P=0.32). There was no significant difference (P=0.098) in GLUT4 protein levels after co-treatment with CoQ10 between any of the treatments and control conditions. Our studies have shown that lipophilic statins (simvastatin) reduce the GLUT4 protein levels in adipocytes, whereas hydrophilic statins (pravastatin) or ezetimibe do not. Co-treatment with CoQ10 appears to prevent the reduction in GLUT4 protein levels caused by simvastatin.