title: Atorvastatin attenuates TNF-α-induced increase of glucose oxidation through PGC-1α upregulation in cardiomyocytes.
abstract: 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 α (TNF-α)-stimulated cardiomyocytes (H9c2 cells) and the potential role of peroxisome proliferation-activated receptor coactivator 1α (PGC-1α) in this effect. Exposure of H9c2 cells to TNF-α inhibited the expressions of PGC-1α, pyruvate dehydrogenase kinase 4, and carnitine palmityl transferase 1 and induced a significant increase in glucose oxidation rate. However, the effects of TNF-α were significantly reversed by atorvastatin. Selective silence of PGC-1α in H9c2 cells resulted in the downregulation of pyruvate dehydrogenase kinase 4 and carnitine palmityl transferase 1 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 upregulation in cardiomyocytes, which might be associated with the regulation of isoprenoid metabolites.
authors.affiliation: Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yinxing
authors.initials: Y
authors.lastname: Ni
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Xingsen
authors.initials: X
authors.lastname: Xu
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.forename: Shanjun
authors.initials: S
authors.lastname: Zhu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000235:genetics*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D011758:Pyrroles; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D005947:Glucose