Title |
Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model
|
---|---|
Published in |
BMC Gastroenterology, April 2015
|
DOI | 10.1186/s12876-015-0269-3 |
Pubmed ID | |
Authors |
Yuichi Nozaki, Koji Fujita, Koichiro Wada, Masato Yoneda, Takaomi Kessoku, Yoshiyasu Shinohara, Kento Imajo, Yuji Ogawa, Makoto Nakamuta, Satoru Saito, Naohiko Masaki, Yoji Nagashima, Yasuo Terauchi, Atsushi Nakajima |
Abstract |
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. 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 8 | 21% |
Researcher | 7 | 18% |
Student > Bachelor | 5 | 13% |
Student > Master | 5 | 13% |
Other | 2 | 5% |
Other | 5 | 13% |
Unknown | 6 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 13 | 34% |
Agricultural and Biological Sciences | 6 | 16% |
Biochemistry, Genetics and Molecular Biology | 5 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 8% |
Unspecified | 1 | 3% |
Other | 2 | 5% |
Unknown | 8 | 21% |