論文 - 詳細
| RRC ID | 27750 |
|---|---|
| 著者 | Moriya T, Kitamori K, Naito H, Yanagiba Y, Ito Y, Yamagishi N, Tamada H, Jia X, Tsuchikura S, Ikeda K, Yamori Y, Nakajima T. |
| タイトル | Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat. |
| ジャーナル | Environ Health Prev Med |
| Abstract |
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 Cu(2+)/Zn(2+)-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 α(1) 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 α(1) type I collagen production and reduced triglyceride synthesis indicated extensive liver fibrosis at 16 weeks in this novel SHRSP5/Dmcr model. |
| 巻・号 | 17(6) |
| ページ | 444-56 |
| 公開日 | 2012-11-1 |
| DOI | 10.1007/s12199-012-0273-y |
| PMID | 22407906 |
| PMC | PMC3493629 |
| MeSH | Animals Biomarkers / blood Blotting, Western Cholesterol / blood Cholesterol, Dietary / adverse effects* Diet, High-Fat / adverse effects* Dietary Fats / blood Disease Models, Animal* Disease Progression Enzyme-Linked Immunosorbent Assay Fatty Liver / blood Fatty Liver / etiology* Fatty Liver / pathology Intercellular Signaling Peptides and Proteins / blood Liver / pathology Liver Cirrhosis / blood Liver Cirrhosis / etiology* Liver Cirrhosis / pathology Male PPAR alpha / blood RNA, Messenger / metabolism Rats* Rats, Inbred SHR Real-Time Polymerase Chain Reaction |
| IF | 2.71 |
| リソース情報 | |
| ラット | SHRSP/5Dmcr(strainID=737) |