Author + information
- Wang Jiang and
- Shanjun Zhu
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 tumour necrosis factor-α (TNF-α)-stimulated cardiomyocytes (H9c2 cells) and the potential role of peroxisome proliferation-activated receptor co-activator -1α (PGC-1α) in this effect.
Exposure of H9c2 cells to TNF-α inhibited the expressions of PGC-1α, pyruvate dehydrogenase kinase 4 (PDK4), carnitine palmityl transferase 1 (CPT1) and induced a significant increase in glucose oxidation rate. However, these effects of TNF-α were significantly reversed by atorvastatin. Selective silence of PGC-1α in H9c2 cells resulted in the down-regulation of PDK4 and CPT1 and further increased the TNF-α-induced glucose oxidation. Interestingly, the effect of atorvastatin on PGC-1α was almost abolished by mevalonate and partially by farnesol, but not by geranylgeraniol.
In conclusion, atorvastatin inhibits TNF-α-induced glucose oxidation through PGC-1α up-regulation in cardiomyocytes, which might be associated with the regulation of isoprenoid metabolites.