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Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids

ABSTRACT: Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids

PROVIDER: PRJNA515481 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8447950_1.fastq.gz	Fastqsanger.gz
	SRR8447950_2.fastq.gz	Fastqsanger.gz
	SRR8447960_1.fastq.gz	Fastqsanger.gz
	SRR8447960_2.fastq.gz	Fastqsanger.gz
	SRR8447951_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids

Project description:RNA sequencing technology was applied to determine the transcriptional changes due to palmitate treatment, RNF213 knockdown, and GPAT4 knockdown.

2019-01-17 | GSE125178 | GEO

Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids.

Project description:Excessive levels of saturated fatty acids are toxic to cells, although the basis for this lipotoxicity remains incompletely understood. Here, we analyzed the transcriptome, lipidome, and genetic interactions of human leukemia cells exposed to palmitate. Palmitate treatment increased saturated glycerolipids, accompanied by a transcriptional stress response, including upregulation of the endoplasmic reticulum (ER) stress response. A comprehensive genome-wide short hairpin RNA (shRNA) screen identified >350 genes modulating lipotoxicity. Among previously unknown genetic modifiers of lipotoxicity, depletion of RNF213, a putative ubiquitin ligase mutated in Moyamoya vascular disease, protected cells from lipotoxicity. On a broader level, integration of our comprehensive datasets revealed that changes in di-saturated glycerolipids, but not other lipid classes, are central to lipotoxicity in this model. Consistent with this, inhibition of ER-localized glycerol-3-phosphate acyltransferase activity protected from all aspects of lipotoxicity. Identification of genes modulating the response to saturated fatty acids may reveal novel therapeutic strategies for treating metabolic diseases linked to lipotoxicity.

| S-EPMC7696670 | biostudies-literature

Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.

Project description:Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.

| S-EPMC4665795 | biostudies-other

Saturated fatty acids induced genes and ISR target genes in pancreatic beta cells

2015-08-01 | GSE49647 | GEO

Saturated fatty acids induced genes and ISR target genes in pancreatic beta cells

Project description:To identify the genes induced by lipotoxicity and integrated stress response in pancreatic beta cells, we have employed whole genome microarray expression in panvreatic beta cell line MIN6m9 cells. First microarray analysis : Wild type MIN6m9 cells were treated with Palmitate, Oleate or negative control condition. Second microarray analysis : Wild type and Fv2E-PERK transgened MIN6m9 cells were treated with mock or artificial dimerizer AP20187(AP) in various time course.

2015-08-01 | E-GEOD-49647 | biostudies-arrayexpress

Saturated fatty acids regulate retinoic acid signaling and suppress tumorigenesis by targeting fatty acid-binding protein 5

Project description:Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes, and precursors for signalling molecules. Here we show that these important biological compounds also regulate gene expression by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARβ/δ. Our data indicates that these activities of LCFA are mediated by FABP5, a protein that delivers ligands from the cytosol to nuclear PPARβ/δ. Both saturated and unsaturated LCFA (SLCFA, ULCFA) tightly bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARβ/δ pathway. By concomitantly promoting the activation of RAR and inhibiting the activity of PPARβ/δ, SLCFA suppress the growth and oncogenic properties of FABP5-expressing carcinoma cells both in cultured cells and in vivo.

2015-09-25 | GSE73186 | GEO

Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids

Project description:Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids

| PRJNA791407 | ENA

RNA-sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate

Project description:Pancreatic beta-cell dysfunction and death are central in the pathogenesis of type 2 diabetes. Saturated fatty acids cause beta-cell failure and contribute to diabetes development in genetically predisposed individuals. Here we used RNA-sequencing to map transcripts expressed in five palmitate-treated human islet preparations, observing 1,325 modified genes. Palmitate induced fatty acid metabolism and endoplasmic reticulum (ER) stress. Functional studies identified novel mediators of adaptive ER stress signaling. Palmitate modified genes regulating ubiquitin and proteasome function, autophagy and apoptosis. Inhibition of autophagic flux and lysosome function contributed to lipotoxicity. Palmitate inhibited transcription factors controlling beta-cell phenotype including PAX4 and GATA6. 59 type 2 diabetes candidate genes were expressed in human islets, and 11 were modified by palmitate. Palmitate modified expression of 17 splicing factors and shifted alternative splicing of 3,525 transcripts. Ingenuity Pathway Analysis of modified transcripts and genes confirmed that top changed functions related to cell death. DAVID analysis of transcription binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA and the ER stress response regulators XBP1 and ATF6. This human islet transcriptome study identified novel mechanisms of palmitate-induced beta-cell dysfunction and death. The data point to crosstalk between metabolic stress and candidate genes at the beta-cell level. 5 human islet of Langerhans preparations examined under 2 conditions (control and palmitate treatment)

2014-01-09 | E-GEOD-53949 | biostudies-arrayexpress

Maternal Diet Enriched with Alpha Linolenic or Saturated Fatty Acids Differentially Regulates Gene Expression in Mice Offspring's liver.

Project description:Lipid metabolic disarray in young and adult mice offspring's liver is induced by saturated fatty acids (SFA) but prevented by alpha linolenic acid (ALA, 18:3 ω3) in the maternal diet during pregnancy and lactation. The aim of the present study was to analyse the impact of maternal dietary ALA on the liver gene expression in the new-born offspring in comparison to a SFA diet. Methods: C57Bl6/J dams were fed with diets normal in calories but rich in ALA or SFA before mating and during pregnancy. Pups were sacrificed at birth and liver parameters were assessed. Gene expression was characterized by microarray analysis and validated by real time qPCR. Results: ALA compared to SFA in maternal diets during pregnancy, increased polyunsaturated fatty acids while differentially modified fatty acid desaturase activities in offspring liver. Overall, 474 and 662 genes from born pups’ liver, were differentially regulated by ALA and SFA compared to control diet (p<0.05; Fold change 2), respectively. Notably, Per3 was up-regulated by ALA whereas down-regulated by SFA, compared to control diet. Conclusions: ALA and SFA enriched diets differentially affect gene expression pattern in the offspring’s liver. ALA in particular, upregulates genes associated to low adiposity.

2018-09-06 | GSE72924 | GEO

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

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 | GSE136271 | GEO

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