RGD Reference Report - Atorvastatin attenuates TNF-alpha-induced increase of glucose oxidation through PGC-1alpha upregulation in cardiomyocytes. - Rat Genome Database

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Atorvastatin attenuates TNF-alpha-induced increase of glucose oxidation through PGC-1alpha upregulation in cardiomyocytes.

Authors: Gao, F  Ni, Y  Luo, Z  Liang, Y  Yan, Z  Xu, X  Liu, D  Wang, J  Zhu, S  Zhu, Z 
Citation: Gao F, etal., J Cardiovasc Pharmacol. 2012 Jun;59(6):500-6. doi: 10.1097/FJC.0b013e31824c853c.
RGD ID: 7242186
Pubmed: PMID:22343369   (View Abstract at PubMed)
DOI: DOI:10.1097/FJC.0b013e31824c853c   (Journal Full-text)

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 1alpha (PGC-1alpha) in this effect. Exposure of H9c2 cells to TNF-alpha inhibited the expressions of PGC-1alpha, 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-1alpha 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-1alpha was almost abolished by mevalonate and partially by farnesol but not by geranylgeraniol. In conclusion, atorvastatin inhibits TNF-alpha-induced glucose oxidation through PGC-1alpha upregulation in cardiomyocytes, which might be associated with the regulation of isoprenoid metabolites.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ppargc1aRatcellular response to tumor necrosis factor  IEP  RGD 
Ppargc1aRatnegative regulation of glycolytic process  IMP  RGD 
Ppargc1aRatresponse to xenobiotic stimulus  IEP atorvastatinRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppargc1a  (PPARG coactivator 1 alpha)


Additional Information