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

Abstract:

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.

journal_name

BMC Gastroenterol

journal_title

BMC gastroenterology

authors

Nozaki Y,Fujita K,Wada K,Yoneda M,Kessoku T,Shinohara Y,Imajo K,Ogawa Y,Nakamuta M,Saito S,Masaki N,Nagashima Y,Terauchi Y,Nakajima A

doi

10.1186/s12876-015-0269-3

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

42

issn

1471-230X

pii

10.1186/s12876-015-0269-3

journal_volume

15

pub_type

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