Journal Article

Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution

Saito, Satoru, Nozaki, Yuichi, Fujita, Koji, Masaki, Naohiko, Nagashima, Yoji, Imajo, Kento, Wada, Koichiro, Nakamuta, Makoto, Shinohara, Yoshiyasu, Kessoku, Takaomi, Ogawa, Yuji, Terauchi, Yasuo, Nakajima, Atsushi, Yoneda, Masato

2015

Overview

Background 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. Methods 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. Results 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. Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Animals / Care and treatment / Carrier Proteins - metabolism / Complications and side effects / Diet, High-Fat - adverse effects / Gastroenterology / Hepatology / Influence / Insulin Resistance / Internal Medicine / Lipid Metabolism / Liver - blood supply / Liver - metabolism / Liver - pathology / Liver diseases / Medicine / Medicine & Public Health / Mice / Mice, Knockout / Morbidity / Nitric oxide / Nitric Oxide Synthase Type III - deficiency / Nitric Oxide Synthase Type III - genetics / Non-alcoholic Fatty Liver Disease - metabolism / Non-alcoholic Fatty Liver Disease - pathology / Research Article / Risk factors