Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model

BMC Gastroenterology

Atsushi Nakajima¹  Yasuo Terauchi⁶  Yoji Nagashima⁵  Naohiko Masaki⁴  Satoru Saito¹  Makoto Nakamuta²  Yuji Ogawa¹  Kento Imajo¹  Yoshiyasu Shinohara¹  Takaomi Kessoku¹  Masato Yoneda¹  Koichiro Wada⁷  Koji Fujita¹  Yuichi Nozaki³ 

[1] Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan;Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, 1-8-1, Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan;Department of Gastroenterology, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Konodai, Ichikawa 272-8516, Japan;Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan;Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan;Department of Pharmacology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan

关键词: NF-kB;    Fibrosis;    Inflammation;    NASH;    NOS;   

Others  :  1177201
DOI  :  10.1186/s12876-015-0269-3

 received in 2014-08-17, accepted in 2015-02-27,  发布年份 2015

【 摘 要 】

Background

Although many of the factors and molecules closely associated with non-alcoholic steatohepatitis (NASH) have been reported, the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) on the progression of NASH remains unclear. We therefore investigated the role of iNOS-derived NO in NASH pathogenesis with a long-term follow-up study using systemic iNOS-knockout mice under high-fat diet (HFD) conditions.

Methods

iNOS-knockout and wild-type mice were fed a basal or HFD for 10 or 48 weeks. Lipid accumulation, fibrosis, and inflammation were evaluated, and various factors and molecules closely associated with NASH were analyzed.

Results

Marked fibrosis and inflammation (indicators of NASH) were observed in the livers of iNOS-knockout mice compared to wild-type mice after 48 weeks of a HFD; however, lipid accumulation in iNOS-knockout mice livers was less than in the wild-type. Increased expressions of various cytokines that are transcriptionally controlled by NF-kB in iNOS-deficient mice livers were observed during HFD conditions.

Conclusions

iNOS-derived NO may play a protective role against the progression to NASH during an HFD by preventing fibrosis and inflammation, which are mediated by NF-kB activation in Kupffer cells. A lack of iNOS-derived NO accelerates progression to NASH without excessive lipid accumulation.

【 授权许可】

   
2015 Nozaki et al.; licensee BioMed Central.

【 图 表 】

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