@phdthesis{oai:nagoya.repo.nii.ac.jp:00014869,
 author = {Moriya, Takashi and Kitamori, Kazuya and Naito, Hisao and Yanagiba, Yukie and Ito, Yuki and Yamagishi, Nozomi and Tamada, Hazuki and Jia, Xiaofang and Tsuchikura, Satoru and Ikeda, Katsumi and Yamori, Yukio and Nakajima, Tamie},
 month = {Nov},
 note = {Objectives: The aim of this study was to identify the molecular mechanisms underlying high-fat and high-cholesterol (HFC) diet-induced steatohepatitis and associated liver fibrosis progression in a novel stroke-prone, spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rat model. Methods: SHRSP5/Dmcr rats were given the control or HFC-diet for 2, 8, and 16 weeks. Plasma and hepatic gene expression of key molecules involved in fatty acid oxidation, inflammation, oxidative stress, and fibrosis were subsequently analyzed. Results: Rats fed the HFC-diet showed increased plasma tumor necrosis factor-α (TNF-α) and hepatic p50/p65 signals, but reduced hepatic Cu2+/Zn2+-superoxide dismutase across the treatment period and reduced plasma total adiponectin at 8 weeks. In HFC-diet-fed rats, transforming growth factor-β1 (TGF-β1) was elevated prior to the appearance of obvious liver fibrosis pathology at 2 weeks, followed by elevations in platelet-derived growth factor-B (PDGF-B) and α-smooth muscle actin (α-SMA), corresponding to evident liver fibrosis, at 8 weeks and by α1 type I collagen production at 16 weeks. The HFC-diet increased hepatic total cholesterol accumulation, although hepatic triglyceride declined by 0.3-fold from 2 to 16 weeks due to reduced hepatic triglyceride synthesis, as suggested by the diacylglycerol acyltransferase 1 and 2 measurements. Conclusions: TNF-α and p50/p65 molecular signals appeared to be major factors for HFC-diet-induced hepatic inflammation and oxidative stress facilitating liver disease progression. While the up-regulation of TGF-β1 prior to the appearance of any evident liver fibrosis could be an early signal for progressive liver fibrosis, elevated PDGF-B and α-SMA levels signified evident liver fibrosis at 8 weeks, and subsequent increased α1 type I collagen production and reduced triglyceride synthesis indicated extensive liver fibrosis at 16 weeks in this novel SHRSP5/Dmcr model., 名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成24年4月27日 森谷隆氏の博士論文として提出された, First published online: 2012-03-10},
 school = {名古屋大学, Nagoya University},
 title = {Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat},
 year = {2012}
}