High-fat and high-cholesterol diet decreases phosphorylated inositol-requiring kinase-1 and inhibits autophagy process in rat liver

Hisao Naito, Yuki Yoshikawa-Bando, Yuan Yuan, Sayuki Hashimoto, Kazuya Kitamori, Hiroshi Yatsuya, Tamie Nakajima

Research output: Contribution to journalArticle

Abstract

Precise molecular pathways involved in the progression of non-alcoholic steatohepatitis (NASH) remain to be elucidated. As Mallory–Denk 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.

Original languageEnglish
Article number12514
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 01-12-2019

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Autophagy
High Fat Diet
Inositol
Phosphotransferases
Cholesterol
Liver
Fatty Liver
Endoplasmic Reticulum Stress
Ubiquitin
Microtubule-Associated Proteins
Heat-Shock Proteins
Endoplasmic Reticulum
Protein Kinases
Proteolysis
Hepatocytes
RNA
Diet
Light

All Science Journal Classification (ASJC) codes

  • General

Cite this

Naito, Hisao ; Yoshikawa-Bando, Yuki ; Yuan, Yuan ; Hashimoto, Sayuki ; Kitamori, Kazuya ; Yatsuya, Hiroshi ; Nakajima, Tamie. / High-fat and high-cholesterol diet decreases phosphorylated inositol-requiring kinase-1 and inhibits autophagy process in rat liver. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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High-fat and high-cholesterol diet decreases phosphorylated inositol-requiring kinase-1 and inhibits autophagy process in rat liver. / Naito, Hisao; Yoshikawa-Bando, Yuki; Yuan, Yuan; Hashimoto, Sayuki; Kitamori, Kazuya; Yatsuya, Hiroshi; Nakajima, Tamie.

In: Scientific reports, Vol. 9, No. 1, 12514, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Kitamori, Kazuya

AU - Yatsuya, Hiroshi

AU - Nakajima, Tamie

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