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Int. J. Mol. Sci. 2015, 16(6), 12213-12229; doi:10.3390/ijms160612213

Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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Academic Editor: Ritva Tikkanen
Received: 24 March 2015 / Revised: 20 May 2015 / Accepted: 21 May 2015 / Published: 29 May 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ), is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD). However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO) C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day) for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice. View Full-Text
Keywords: pioglitazone; non-alcoholic fatty liver disease; Affymetrix Mouse GeneChip; inflammation response; lipid metabolism pioglitazone; non-alcoholic fatty liver disease; Affymetrix Mouse GeneChip; inflammation response; lipid metabolism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Jia, C.; Huan, Y.; Liu, S.; Hou, S.; Sun, S.; Li, C.; Liu, Q.; Jiang, Q.; Wang, Y.; Shen, Z. Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice. Int. J. Mol. Sci. 2015, 16, 12213-12229.

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