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As Mallory\u2013Denk bodies were occasionally observed in the enlarged hepatocytes in NASH model rat (SHRSP5\/Dmcr) fed high-fat and high-cholesterol (HFC) diet, we aimed to clarify the roles of autophagy and endoplasmic reticulum (ER) stress in NASH progression. Male SHRSP5\/Dmcr were randomly divided into 4 groups. Two groups were fed a control diet; the other two groups were fed a HFC diet for 2 and 8 weeks, respectively. The HFC diet increased the autophagy-related proteins levels and microtubule-associated protein 1 light chain 3-II\/I ratio after 2 and 8 weeks, respectively. However, regarding ER stress-related proteins, the HFC diet decreased the levels of phosphorylated (p-) inositol-requiring kinase-1 (p-IRE-1) and p-protein kinase RNA-like ER kinase after 2 weeks. Additionally, the HFC diet increased anti-ubiquitin-positive cells and the level of the autophagy substrate p62, suggesting that the HFC diet induced dysfunction in ubiquitin-dependent protein degradation pathways. In conclusion, the HFC diet arrested the autophagy process in the liver; this was particularly associated with decreases in p-IRE-1 expression.<\/jats:p>","DOI":"10.1038\/s41598-019-48973-w","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T10:03:26Z","timestamp":1567073006000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["High-fat and high-cholesterol diet decreases phosphorylated inositol-requiring kinase-1 and inhibits autophagy process in rat liver"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4228-637X","authenticated-orcid":false,"given":"Hisao","family":"Naito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Yoshikawa-Bando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayuki","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Kitamori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Yatsuya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0474-7019","authenticated-orcid":false,"given":"Tamie","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,8,29]]},"reference":[{"key":"48973_CR1","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1056\/NEJMra011775","volume":"346","author":"P Angulo","year":"2002","unstructured":"Angulo, P. 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