Western diet-induced hepatic steatosis and alterations in the liver transcriptome in adult Brown-Norway rats View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-10-30

AUTHORS

Michael D. Roberts, C. Brooks Mobley, Ryan G. Toedebush, Alexander J. Heese, Conan Zhu, Anna E. Krieger, Clayton L. Cruthirds, Christopher M. Lockwood, John C. Hofheins, Charles E. Wiedmeyer, Heather J. Leidy, Frank W. Booth, R. Scott Rector

ABSTRACT

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. More... »

PAGES

151

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12876-015-0382-3

DOI

http://dx.doi.org/10.1186/s12876-015-0382-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008242302

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26519296


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23 schema: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.
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31 Brown Norway male rats
32 NAFLD development
33 Norway
34 Norway male rats
35 RNA deep sequencing
36 WD
37 WD feeding
38 WD-fed rats
39 Western diet-induced hepatic steatosis
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41 acute phase response genes
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43 adult Brown Norway
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46 biochemistry
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53 deep sequencing
54 desaturase (Scd) mRNA expression
55 development
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59 disease
60 disease development
61 early nonalcoholic fatty liver disease (NAFLD) development
62 early stages
63 effect
64 expression
65 fat
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67 feeding
68 findings
69 gene networks
70 genes
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72 hepatic steatosis development
73 high fat
74 high-sucrose diet feeding
75 increase
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77 inflammation
78 inflammation-related liver transcripts
79 levels
80 libitum access
81 lipid metabolism
82 literature
83 liver
84 liver disease
85 liver disease development
86 liver inflammation
87 liver stearoyl-CoA desaturase (Scd) mRNA expression
88 liver transcriptome
89 liver transcripts
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91 mRNA expression
92 male rats
93 metabolism
94 mineral metabolism
95 molecular biochemistry
96 network
97 nonalcoholic fatty liver disease (NAFLD) development
98 overt liver inflammation
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101 phase response genes
102 previous literature
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111 steatosis
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115 sub-chronic high fat
116 sucrose diet (also termed 'Westernized diet' or WD) feeding
117 summary
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120 tendency
121 top
122 transcriptome
123 transcripts
124 triacylglycerol content
125 vitamin
126 weeks
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