Peroxisome proliferator-activated receptor alpha protects against obesity-induced hepatic inflammation

Stienstra, Rinke, Mandard, Stéphane, Patsouris, David, Maass, Cathy, Kersten, Sander and Müller, Michael (2007) Peroxisome proliferator-activated receptor alpha protects against obesity-induced hepatic inflammation. Endocrinology, 148 (6). pp. 2753-63. ISSN 0013-7227

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Abstract

Recently it has become evident that obesity is associated with low-grade chronic inflammation. The transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) has been shown to have a strong antiinflammatory action in liver. However, the role of PPARalpha in obesity-induced inflammation is much less clear. Therefore, the aim of our study was to determine whether PPARalpha plays a role in obesity-induced hepatic inflammation. To induce obesity, wild-type sv129 and PPARalpha(-/-) mice were exposed to a chronic high-fat diet (HFD), using a low-fat diet (LFD) as control. In wild-type mice, HFD significantly increased the hepatic and adipose expression of numerous genes involved in inflammation. Importantly, this effect was amplified in PPARalpha(-/-) mice, suggesting an antiinflammatory role of PPARalpha in liver and adipose tissue. Further analysis identified specific chemokines and macrophage markers, including monocyte chemotactic protein 1 and F4/80(+), that were elevated in liver and adipose tissue of PPARalpha(-/-) mice, indicating increased inflammatory cell recruitment in the knockout animals. When all groups of mice were analyzed together, a significant correlation between hepatic triglycerides and expression of inflammatory markers was observed. Many inflammatory genes that were up-regulated in PPARalpha(-/-) livers by HFD were down-regulated by treatment with the PPARalpha ligand Wy-14643 under normal nonsteatotic conditions, either in vivo or in vitro, suggesting an antiinflammatory effect of PPARalpha that is independent of reduction in liver triglycerides. In conclusion, our results suggest that PPARalpha protects against obesity-induced chronic inflammation in liver by reducing hepatic steatosis, by direct down-regulation of inflammatory genes, and by attenuating inflammation in adipose tissue.

Item Type: Article
Uncontrolled Keywords: adipose tissue,animals,cells, cultured,diet, atherogenic,diet, fat-restricted,gene expression profiling,gene expression regulation,hepatitis, animal,liver,male,mice,mice, knockout,obesity,oligonucleotide array sequence analysis,ppar alpha,reverse transcriptase polymerase chain reaction,triglycerides
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 07 Jul 2014 12:02
Last Modified: 21 Apr 2020 22:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/47723
DOI: 10.1210/en.2007-0014

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