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| Status |
Public on Aug 27, 2019 |
| Title |
Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [3T3-L1] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
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| Overall design |
3T3-L1 pre-adipocytes were incubated with 3 different fatty acids and control for 24hrs, whereafter gene expression profiling was performed.
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| Contributor(s) |
Oteng A, Loregger A, van Weeghel M, Zelcer N, Kersten S |
| Citation(s) |
31327168 |
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| Submission date |
Aug 26, 2019 |
| Last update date |
Aug 29, 2019 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE136354 |
Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease |
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| Relations |
| BioProject |
PRJNA562280 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE136351_RAW.tar |
19.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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