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- Title
Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution.
- Authors
Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Kessoku, Takaomi; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi
- Abstract
<bold>Background: </bold>Although many factors and molecules that are closely associated with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported, the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in the pathogenesis of NAFLD/NASH remains unclear. We therefore investigated the role of eNOS-derived NO in NAFLD pathogenesis using systemic eNOS-knockout mice fed a high-fat diet.<bold>Methods: </bold>eNOS-knockout and wild-type mice were fed a basal diet or a high-fat diet for 12 weeks. Lipid accumulation and inflammation were evaluated in the liver, and various factors that are closely associated with NAFLD/NASH and hepatic tissue blood flow were analyzed.<bold>Results: </bold>Lipid accumulation and inflammation were more extensive in the liver and lipid accumulation was less extensive in the visceral fat tissue in eNOS-knockout mice, compared with wild-type mice, after 12 weeks of being fed a high-fat diet. While systemic insulin resistance was comparable between the eNOS-knockout and wild-type mice fed a high-fat diet, hepatic tissue blood flow was significantly suppressed in the eNOS-knockout mice, compared with the wild-type mice, in mice fed a high-fat diet. The microsomal triglyceride transfer protein activity was down-regulated in eNOS-knockout mice, compared with wild-type mice, in mice fed a high-fat diet.<bold>Conclusions: </bold>A deficiency of eNOS-derived NO may exacerbate the early-stage of NASH pathogenesis by changing the fat distribution in a mouse model via the regulation of hepatic tissue blood flow.
- Subjects
NITRIC-oxide synthases; ENDOTHELIAL cells; FATTY liver; KNOCKOUT mice; HIGH-fat diet; INFLAMMATION; LIPIDS in the body; BLOOD flow; ANIMALS; CARRIER proteins; DIET; GENETIC disorders; INSULIN resistance; LIPID metabolism disorders; LIVER; MICE; OXIDOREDUCTASES
- Publication
BMC Gastroenterology, 2015, Vol 15, p1
- ISSN
1471-230X
- Publication type
journal article
- DOI
10.1186/s12876-015-0409-9