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Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats
BACKGROUND: The purpose of this study was to investigate the effects of sub-chronic high fat, high sucrose diet (also termed ‘Westernized diet’ or WD) feeding on the liver transcriptome during early nonalcoholic fatty liver disease (NAFLD) development. METHODS: Brown Norway male rats (9 months of ag...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628330/ https://www.ncbi.nlm.nih.gov/pubmed/26519296 http://dx.doi.org/10.1186/s12876-015-0382-3 |
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author | Roberts, Michael D. Mobley, C. Brooks Toedebush, Ryan G. Heese, Alexander J. Zhu, Conan Krieger, Anna E. Cruthirds, Clayton L. Lockwood, Christopher M. Hofheins, John C. Wiedmeyer, Charles E. Leidy, Heather J. Booth, Frank W. Rector, R. Scott |
author_facet | Roberts, Michael D. Mobley, C. Brooks Toedebush, Ryan G. Heese, Alexander J. Zhu, Conan Krieger, Anna E. Cruthirds, Clayton L. Lockwood, Christopher M. Hofheins, John C. Wiedmeyer, Charles E. Leidy, Heather J. Booth, Frank W. Rector, R. Scott |
author_sort | Roberts, Michael D. |
collection | PubMed |
description | BACKGROUND: The purpose of this study was to investigate the effects of sub-chronic high fat, high sucrose diet (also termed ‘Westernized diet’ or WD) feeding on the liver transcriptome during early nonalcoholic fatty liver disease (NAFLD) development. METHODS: Brown Norway male rats (9 months of age) were randomly assigned to receive ad libitum access to a control (CTL; 14 % kcal fat, 1.2 % sucrose by weight) diet or WD (42 % kcal from fat, 34 % sucrose by weight) for 6 weeks. RESULTS: Six weeks of WD feeding caused hepatic steatosis development as evidenced by the 2.25-fold increase in liver triacylglycerol content, but did not induce advanced liver disease (i.e., no overt inflammation or fibrosis) in adult Brown Norway rats. RNA deep sequencing (RNA-seq) revealed that 94 transcripts were altered in liver by WD feeding (46 up-, 48 down-regulated, FDR < 0.05). Specifically, the top differentially regulated gene network by WD feeding was ‘Lipid metabolism, small molecular biochemistry, vitamin and mineral metabolism’ (Ingenuity Pathway Analysis (IPA) score 61). The top-regulated canonical signaling pathway in WD-fed rats was the ‘Superpathway of cholesterol biosynthesis’ (10/29 genes regulated, p = 1.68E-17), which coincides with a tendency for serum cholesterol levels to increase in WD-fed rats (p = 0.09). Remarkably, liver stearoyl-CoA desaturase (Scd) mRNA expression was by far the most highly-induced transcript in WD-fed rats (approximately 30-fold, FDR = 0.01) which supports previous literature underscoring this gene as a crucial target during NAFLD development. CONCLUSIONS: In summary, sub-chronic WD feeding appears to increase hepatic steatosis development over a 6-week period but only induces select inflammation-related liver transcripts, mostly acute phase response genes. These findings continue to outline the early stages of NAFLD development prior to overt liver inflammation and advanced liver disease. |
format | Online Article Text |
id | pubmed-4628330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46283302015-11-01 Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats Roberts, Michael D. Mobley, C. Brooks Toedebush, Ryan G. Heese, Alexander J. Zhu, Conan Krieger, Anna E. Cruthirds, Clayton L. Lockwood, Christopher M. Hofheins, John C. Wiedmeyer, Charles E. Leidy, Heather J. Booth, Frank W. Rector, R. Scott BMC Gastroenterol Research Article BACKGROUND: The purpose of this study was to investigate the effects of sub-chronic high fat, high sucrose diet (also termed ‘Westernized diet’ or WD) feeding on the liver transcriptome during early nonalcoholic fatty liver disease (NAFLD) development. METHODS: Brown Norway male rats (9 months of age) were randomly assigned to receive ad libitum access to a control (CTL; 14 % kcal fat, 1.2 % sucrose by weight) diet or WD (42 % kcal from fat, 34 % sucrose by weight) for 6 weeks. RESULTS: Six weeks of WD feeding caused hepatic steatosis development as evidenced by the 2.25-fold increase in liver triacylglycerol content, but did not induce advanced liver disease (i.e., no overt inflammation or fibrosis) in adult Brown Norway rats. RNA deep sequencing (RNA-seq) revealed that 94 transcripts were altered in liver by WD feeding (46 up-, 48 down-regulated, FDR < 0.05). Specifically, the top differentially regulated gene network by WD feeding was ‘Lipid metabolism, small molecular biochemistry, vitamin and mineral metabolism’ (Ingenuity Pathway Analysis (IPA) score 61). The top-regulated canonical signaling pathway in WD-fed rats was the ‘Superpathway of cholesterol biosynthesis’ (10/29 genes regulated, p = 1.68E-17), which coincides with a tendency for serum cholesterol levels to increase in WD-fed rats (p = 0.09). Remarkably, liver stearoyl-CoA desaturase (Scd) mRNA expression was by far the most highly-induced transcript in WD-fed rats (approximately 30-fold, FDR = 0.01) which supports previous literature underscoring this gene as a crucial target during NAFLD development. CONCLUSIONS: In summary, sub-chronic WD feeding appears to increase hepatic steatosis development over a 6-week period but only induces select inflammation-related liver transcripts, mostly acute phase response genes. These findings continue to outline the early stages of NAFLD development prior to overt liver inflammation and advanced liver disease. BioMed Central 2015-10-30 /pmc/articles/PMC4628330/ /pubmed/26519296 http://dx.doi.org/10.1186/s12876-015-0382-3 Text en © Roberts et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Roberts, Michael D. Mobley, C. Brooks Toedebush, Ryan G. Heese, Alexander J. Zhu, Conan Krieger, Anna E. Cruthirds, Clayton L. Lockwood, Christopher M. Hofheins, John C. Wiedmeyer, Charles E. Leidy, Heather J. Booth, Frank W. Rector, R. Scott Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats |
title | Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats |
title_full | Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats |
title_fullStr | Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats |
title_full_unstemmed | Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats |
title_short | Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats |
title_sort | western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult brown-norway rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628330/ https://www.ncbi.nlm.nih.gov/pubmed/26519296 http://dx.doi.org/10.1186/s12876-015-0382-3 |
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