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

Gao, Feng MD*; Ni, Yinxing MD; Luo, Zhidan MD; Liang, Yi MS; Yan, Zhencheng MD; Xu, Xingsen MD; Liu, Daoyan PhD; Wang, Jiang MD*; Zhu, Shanjun MD, PhD*; Zhu, Zhiming MD, PhD

Journal of Cardiovascular Pharmacology: June 2012 - Volume 59 - Issue 6 - p 500–506
doi: 10.1097/FJC.0b013e31824c853c
Original Article
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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.

*Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China

Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing, China.

Reprints: Shanjun Zhu, MD, PhD, and Jiang Wang, MD, Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China (e-mail: zhuzm@yahoo.com).

F. Gao and Y. Ni contribute to this work equally.

Supported by grants for Natural Science Foundation of China (No. 30971229 and 30890042) and the Grant of National Key Basic Research and Development Plan of China (No. 2011CB503902).

The authors declare no conflicts of interest.

Received September 26, 2011

Accepted January 23, 2012

© 2012 Lippincott Williams & Wilkins, Inc.