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Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [3T3-L1]

ABSTRACT: Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [3T3-L1]

PROVIDER: PRJNA562280 | ENA |

REPOSITORIES: ENA

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Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [3T3-L1]

Project description: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.

2019-08-27 | GSE136351 | GEO

Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease

Project description:Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease

| PRJNA562281 | ENA

Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [liver]

Project description:Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [liver]

| PRJNA561813 | ENA

Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [liver]

2019-08-27 | GSE136271 | GEO

Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [Hepa1-6 cells]

2019-08-27 | GSE136278 | GEO

Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [Hepa1-6 cells]

Project description:Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease [Hepa1-6 cells]

| PRJNA561817 | ENA

Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease.

Project description:ScopeThe mechanisms underlying the deleterious effects of trans fatty acids on plasma cholesterol and non-alcoholic fatty liver disease (NAFLD) are unclear. Here, the aim is to investigate the molecular mechanisms of action of industrial trans fatty acids.Methods and resultsHepa1-6 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 shows that elaidate but not oleate or palmitate induces expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate is mediated by increased sterol regulatory element-binding protein 2 (SREBP2) activity and is dependent on SREBP cleavage-activating protein (SCAP), yet independent of liver-X receptor and ubiquitin regulatory X domain-containing protein 8. Elaidate decreases intracellular free cholesterol levels and represses the anticholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increases the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, alanine aminotransferase activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets.ConclusionElaidate induces cholesterogenesis in vitro by activating the SCAP-SREBP2 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.

| S-EPMC6790681 | biostudies-literature

Industrial trans fatty acids stimulate SREBP2-mediated cholesterogenesis and promote non-alcoholic fatty liver disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-08-27 | GSE136354 | GEO

Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colonocytes by selective PPARγ modulation

Project description:Angiopoietin-like protein 4 (ANGPTL4, also referred to as Fiaf) has been proposed as a circulating mediator between the gut microbiota and fat storage in adipose tissue. Very little is known about the mechanisms of regulation of ANGPTL4 in the colon. Here we show that transcription and subsequent secretion of ANGPTL4 in human T84 and HT-29 colonocytes is highly induced by physiological concentrations of products of bacterial fermentation, the short-chain fatty acids. Short-chain fatty acids induce ANGPTL4 by activating the nuclear receptor PPARγ, as shown by microarray, transactivation assays, coactivator peptide recruitment assay, and use of PPARγ antagonist. At concentrations required for PPARγ activation and ANGPTL4 induction in colonocytes, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modelling. It can be concluded that 1) SCFA potently stimulate ANGPTL4 synthesis in human colonocytes, and 2) SCFA transactivate and bind to PPARγ by serving as selective PPAR modulators. Our data point to activation of PPARγ as a novel mechanism of gene regulation by SCFA in the colon.

2013-03-11 | GSE40706 | GEO

Effects of Intestine-specifc SREBP2 overactivation on gene expression in mouse jejnum

Project description:The active form of the SREBP2 transcription factor was specifically overexpressed in the intesitne. This was achieved by generating transgenic mouse model (designated as ISR2) in which the transgene represents the N-terminal active SREBP2 transcription factor driven by the villin promoter. In this project, we investigated the effects of overactivation of SREBP2 on gene expression in mouse jejunum Gene expression profile in the jejunum of ISR2 was compared to gene expression profile in the jejunum of their wild type littermates.

2013-10-26 | E-GEOD-51736 | biostudies-arrayexpress

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