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World J Gastroenterol. Dec 21, 2008; 14(47): 7240-7246
Published online Dec 21, 2008. doi: 10.3748/wjg.14.7240
Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease
Hai-Ning Wang, Yan-Rong Wang, Guo-Qiang Liu, Zhe Liu, Pei-Xian Wu, Xiao-Ling Wei, Tian-Pei Hong
Hai-Ning Wang, Yan-Rong Wang, Guo-Qiang Liu, Zhe Liu, Pei-Xian Wu, Xiao-Ling Wei, Tian-Pei Hong, Department of Endocrinology, Peking University Third Hospital, Beijing 100191, China
Author contributions: Wang HN and Wang YR contributed equally to this work. Wang YR and Hong TP designed the research; Wang HN, Liu Z, Wu PX, and Wei XL performed the research; Hong TP, Wang HN and Liu GQ analyzed the data and wrote the paper.
Supported by The National Natural Science Foundation of China, No. 30771032 and No. 30700879, the National 973 Program of China, No. 2006CB503900, the National 863 Program of China, No. 2006AA02A112, and the Natural Science Foundation of Beijing City, No. 7062067
Correspondence to: Tian-Pei Hong, MD, PhD, Professor, Department of Endocrinology, Peking University Third Hospital, Beijing 100191, China. tpho66@bjmu.edu.cn
Telephone: +86-10-82265515 Fax: +86-10-62017700
Received: August 25, 2008
Revised: November 11, 2008
Accepted: November 18, 2008
Published online: December 21, 2008
Abstract

AIM: To investigate the effects of rosiglitazone (RGZ) on expression of interleukin-18 (IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease (NAFLD) rats.

METHODS: Twenty-eight Sprague-Dawley (SD) rats were randomly divided into control, NAFLD, and RGZ treated NAFLD groups. A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk. The NAFLD animals were treated with RGZ or vehicle for the last 4 wk (week 9-12) and then sacrificed to obtain liver tissues. Histological changes were analyzed with HE, oil red O and Masson’s trichrome staining. Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis.

RESULTS: The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group. Steatosis, inflammation and fibrosis, found in the liver of NAFLD rats, were significantly improved 4 wk after RGZ treatment. The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.

CONCLUSION: RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats. The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.

Keywords: Insulin resistance; Interleukin-18; Non-alcoholic fatty liver; Rosiglitazone