Dataset Information

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

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.

SUBMITTER: Naito H

PROVIDER: S-EPMC6715744 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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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 H Yoshikawa-Bando Yuki Y Yuan Yuan Y Hashimoto Sayuki S Kitamori Kazuya K Yatsuya Hiroshi H Nakajima Tamie T

Scientific reports 20190829 1

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 ...[more]

PMID: 31467308

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Project description:High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma β-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver. Adult male Wistar rats were fed diets with varying amounts of protein, carbohydrates and fat for 5 weeks. At the end of the experiment, rats were killed and tanscriptome analysis was performed on pooled liver samples.

Dataset Information

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

Publications

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

Similar Datasets

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