Atorvastatin Attenuates TNF-α-induced Increase of Glucose Oxidation Through PGC-1α Upregulation in Cardiomyocytes

Recent studies have shown that atorvastain has anti-inflammatory effect and can prevent cardiac hypertrophy. The development of cardiac hypertrophy and dysfunction is associated with an increase in cardiac glucose utilization. In this study, we investigated the effect of atorvastatin on glucose oxidation in tumor necrosis factor alpha (TNF-alpha)-stimulated cardiomyocytes (H9c2 cells) and the potential role of peroxisome proliferation-activated receptor coactivator 1 alpha (PGC-1 alpha) in this effect. Exposure of H9c2 cells to TNF-alpha inhibited the expressions of PGC-1 alpha, pyruvate dehydrogenase kinase 4, and carnitine palmityl transferase 1 and induced a significant increase in glucose oxidation rate. However, the effects of TNF-alpha were significantly reversed by atorvastatin. Selective silence of PGC-1 alpha in H9c2 cells resulted in the downregulation of pyruvate dehydrogenase kinase 4 and carnitine palmityl transferase 1 and further increased the TNF-alpha-induced glucose oxidation. Interestingly, the effect of atorvastatin on PGC-1 alpha was almost abolished by mevalonate and partially by farnesol but not by geranylgeraniol. In conclusion, atorvastatin inhibits TNF-alpha-induced glucose oxidation through PGC-1 alpha upregulation in cardiomyocytes, which might be associated with the regulation of isoprenoid metabolites.