Free fatty acids and TNF-alpha in hepg2/c3a cell culture
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE5441 | GEO | 2006/08/04
SECONDARY ACCESSION(S): PRJNA96109
REPOSITORIES: GEO
Similar Datasets
Project description:The regulation of complex cellular activities in palmitate treated HepG2 cells, and the ensuing cytotoxic phenotype, involves cooperative interactions between genes. While previous approaches have largely focused on identifying individual target genes, elucidating interacting genes has thus far remained elusive. We applied the concept of information synergy to reconstruct a ?gene-cooperativity? network for palmititate-induced cytotoxicity in liver cells. Our approach integrated gene expression data with metabolic profiles to select a subset of genes for network reconstruction. Subsequent analysis of the network revealed insulin signaling as the most significantly enriched pathway, and desmoplakin (DSP) as its top neighbor. We determined that palmitate significantly reduces DSP expression, and treatment with insulin restores the lost expression of DSP. Insulin resistance is a common pathological feature of fatty liver and related ailments, whereas loss of DSP has been noted in liver carcinoma. Reduced DSP expression can lead to loss of cell-cell adhesion via desmosomes, and disrupt the keratin intermediate filament network. Our findings suggest that DSP expression may be perturbed by palmitate and, along with insulin resistance, may play a role in palmitate induced cytotoxicity, and serve as potential targets for further studies on non-alcoholic fatty liver disease (NAFLD). free fatty acids(palmitate, oleate, linoleate) 0.7mM and tnf-alpha (0 20,100 ng/ml) were subjected to HepG2 cell line to study the cytotoxicity induced by these two factors. control(Hepg2 medium and BSA medium) treatment(combinations of TNFa+FFAs) two biological replicates for each condition, color swap for each sample
2012-05-01 | E-GEOD-26885 | biostudies-arrayexpress
Project description:Diabetes mellitus, obesity, and dyslipidemia increase risk for cardiovascular disease, and expose the heart to high plasma fatty acid (FA) levels. Recent studies suggest that distinct FA species are cardiotoxic (e.g., palmitate), while others are cardioprotective (e.g., oleate), although the molecular mechanisms mediating these observations are unclear. The purpose of the present study was to investigate the differential effects of distinct FA species (varying carbon length and degree of saturation) on adult rat cardiomyocyte (ARC) gene expression. ARCs were initialy challenged with 0.4 mM octanoate (8:0), palmitate (16:0), stearate (18:0), oleate (18:1), or linoleate (18:2) for 24 h. Microarray analysis revealed differential regulation of gene expression by the distinct FAs; the order regarding the number of genes whose expression was influenced by a specific FA was octanoate (1,188) . stearate (740) . palmitate (590) . oleate (83) . linoleate (65). In general, cardioprotective FAs (e.g., oleate) increased expression of genes promoting FA oxidation to a greater extent than cardiotoxic FAs (e.g., palmitate), whereas the latter induced markers of endoplasmic reticulum and oxidative stress. Subsequent RT-PCR analysis revealed distinct time- and concentration-dependent effects of these FA species, in a gene-specific manner. For example, stearate- and palmitate-mediated ucp3 induction tended to be transient (i.e., initial high induction, followed by subsequent repression), whereas oleate-mediated induction was sustained. These findings may provide insight into why diets high in unsaturated FAs (e.g., oleate) are cardioprotective, whereas diets rich in saturated FAs (e.g., palmitate) are not.
2010-03-24 | GSE21023 | GEO
Project description:The regulation of complex cellular activities in palmitate treated HepG2 cells, and the ensuing cytotoxic phenotype, involves cooperative interactions between genes. While previous approaches have largely focused on identifying individual target genes, elucidating interacting genes has thus far remained elusive. We applied the concept of information synergy to reconstruct a ?gene-cooperativity? network for palmititate-induced cytotoxicity in liver cells. Our approach integrated gene expression data with metabolic profiles to select a subset of genes for network reconstruction. Subsequent analysis of the network revealed insulin signaling as the most significantly enriched pathway, and desmoplakin (DSP) as its top neighbor. We determined that palmitate significantly reduces DSP expression, and treatment with insulin restores the lost expression of DSP. Insulin resistance is a common pathological feature of fatty liver and related ailments, whereas loss of DSP has been noted in liver carcinoma. Reduced DSP expression can lead to loss of cell-cell adhesion via desmosomes, and disrupt the keratin intermediate filament network. Our findings suggest that DSP expression may be perturbed by palmitate and, along with insulin resistance, may play a role in palmitate induced cytotoxicity, and serve as potential targets for further studies on non-alcoholic fatty liver disease (NAFLD).
2012-05-02 | GSE26885 | GEO
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
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
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
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 | GSE136278 | GEO
Project description:Macrophages from wild type or knockout mice with various treatments [none, BSA (control), palmitate + oleate, conditioned media from adipocytes treated with either BSA or palmitate + oleate). N=4/group.
2017-06-05 | ST000684 | MetabolomicsWorkbench
Project description:Macrophages from wild type or knockout mice with various treatments [none, BSA (control), palmitate + oleate, conditioned media from adipocytes treated with either BSA or palmitate + oleate). N=4/group.
2018-08-02 | MSV000082722 | GNPS
Project description:A global transcriptomic study enables investigating human skeletal muscle gene targets of palmitate versus oleate and the capacity of oleate to alter palmitate-effects.
2015-12-01 | GSE53116 | GEO