Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue

Liver International - Tập 29 Số 7 - Trang 988-996 - 2009
Hiroshi Kudo1, Yutaka Yata2,1, Terumi Takahara1, Kengo Kawai1, Yasuhiro Nakayama1, Masami Kanayama1, Takeshi Oya3, Seiichi Morita4, Masakiyo Sasahara3, Derek A. Mann5, Toshiro Sugiyama1
1Third Department of Internal Medicine, University of Toyama, Toyama, Japan
2Saiseikai-Maebashi Hospital, Gunma, Japan
3Department of Pathology, University of Toyama, Toyama, Japan
4Second Department of Surgery, University of Toyama, Toyama, Japan
5Liver Group, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK

Tóm tắt

AbstractBackground/Aims: Non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis (NASH) are the hepatic manifestation of metabolic syndrome. However, its therapeutic strategy has not been established. Recently, an angiotensin II type 1 receptor blocker, telmisartan (Tel), has received a great deal of attention as a therapeutic tool for metabolic syndrome. The aim of this study was to investigate the efficacy and mechanisms of Tel on a murine NASH model.Methods: C57BL/6 mice were fed a methionine‐ and choline‐deficient high‐fat diet (MCDHF) or a standard diet with/without the administration of Tel (10 mg/kg/day) for 8 weeks.Results: MCDHF feeding induced marked steatohepatitis with macrophage infiltration. Tel attenuated liver steatosis with decreased hepatic triglycerides (P<0.05) and fibrogenesis with decreased type I collagen and transforming growth factor‐β1 mRNA expressions (P<0.05). Tel also suppressed the infiltration of macrophages into the liver and decreased hepatic monocyte chemoattractant protein‐1 and its receptor (CC‐chemokine receptor 2; CCR2) mRNA expressions, especially CCR2. In vitro, Tel suppressed CCR2 expression, which was induced by low‐density lipoprotein. The size of adipocyte in visceral fat tissue was reduced with an increased serum adiponectin concentration in the Tel group.Conclusions: In this study, we revealed that Tel attenuated steatohepatitis progression by suppressing the macrophage infiltration into the liver. Tel also affected the reduction of adipocyte size and elevation of serum adiponectin. Tel might serve as a new therapeutic strategy for NASH.

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Liver International

Tập 29 Số 7

988-996

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