MRNAseq of primary hepatocytes treated in vitro with Itaconate, Lipid, or Itaconate + Lipid
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA947249 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23934100_1.fastq.gz | Fastqsanger.gz | |||
| SRR23934100_2.fastq.gz | Fastqsanger.gz | |||
| SRR23934101_1.fastq.gz | Fastqsanger.gz | |||
| SRR23934101_2.fastq.gz | Fastqsanger.gz | |||
| SRR23934102_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description:primary hepatocytes isolated from wildtype mouse livers and treated overnight in complete media with 10mM sodium itaconate in the presence or absence of a 1:10 dilution of sterile, chemically defined lipid mixture 1 (Sigma-Aldrich)
2023-03-28 | GSE227900 | GEO
Project description:One primary metabolic manifestation of inflammation is the diversion of cis-aconitate within the tricarboxylic acid (TCA) cycle to synthesize the immunometabolite itaconate. Itaconate is well established to possess immunomodulatory and metabolic effects within myeloid cells and lymphocytes, however, its effects in other organ systems during sepsis remain less clear. Utilizing Irg1 knockout mice that are deficient in synthesizing itaconate, we aimed at understanding the metabolic role of itaconate in the liver and systemically during sepsis. We find itaconate aids in lipid metabolism during sepsis. Specifically, Irg1 KO mice develop a heightened level of hepatic steatosis when induced with polymicrobial sepsis. Proteomics analysis reveal enhanced expression of enzymes involved in fatty acid oxidation in following 4-ocytl itaconate (4-OI) treatment in vitro. Downstream analysis reveals itaconate stabilizes the expression of the mitochondrial fatty acid uptake enzyme CPT1a, mediated by its hypoubiquitination. Chemoproteomic analysis revealed itaconate interacts with proteins involved in protein ubiquitination as a potential mechanism underlying its stabilizing effect on CPT1a. From a systemic perspective, we find itaconate deficiency triggers a hypothermic response following endotoxin stimulation, potentially mediated by brown adipose tissue (BAT) dysfunction. Finally, by use of metabolic cage studies, we demonstrate Irg1 KO mice rely more heavily on carbohydrates versus fatty acid sources for systemic fuel utilization in response to endotoxin treatment. Our data reveal a novel metabolic role of itaconate in modulating fatty acid oxidation during polymicrobial sepsis.
2024-01-29 | PXD047706 | Pride
Project description:Itaconate is an immunoregulatory metabolite produced by the mitochondrial enzyme immune-responsive gene 1 (IRG1) in inflammatory macrophages. We recently identified an important mechanism by which itaconate is released from inflammatory macrophages. However, it remains unknown whether extracellular itaconate is taken up by non-myeloid cells to exert immunoregulatory functions. Here, we used a custom-designed CRISPR screen to identify the dicarboxylate transporter solute carrier family 13 member 3 (SLC13A3) as an itaconate importer and to characterize the role of SLC13A3 in itaconate-improved hepatic antibacterial innate immunity. Functionally, liver-specific deletion of Slc13a3 impairs hepatic antibacterial innate immunity in vivo and in vitro. Mechanistically, itaconate uptake via SLC13A3 induces transcription factor EB (TFEB)-dependent lysosomal biogenesis and subsequently improves antibacterial innate immunity in murine hepatocytes. These findings identify SLC13A3 as a key itaconate importer in murine hepatocytes and will aid in the development of potent itaconate-based antibacterial therapeutics.
2024-07-08 | GSE230735 | GEO
Project description:Objective: Benzbromarone (BBR) is an effective uric acid-lowering drug, and studies have shown that BBR can exacerbate hepatic steatosis in obese individuals. However, the underlying mechanisms remain unclear. Methods: Primary hepatocytes isolated from C57/BL6 mice were cultured in vitro, and a high-fat culture model was simulated with 20mM oleic acid (OA) treatment. OA and bovine serum albumin (BSA) were mixed at a ratio of 1:4, pre-treated at 37°C for 1-2 hours, and then co-incubated with primary hepatocytes for 16 hours. The in vitro experiments were divided into four groups: control (BSA), control treatment group (BSA+BBR), high-fat group (OA), and high-fat treatment group (OA+BBR). After 16 hours of treatment, intracellular triglyceride (TAG) content was measured, and Bodipy staining was used to observe the number and morphological changes of lipid droplets. RNA-seq analysis was conducted to assess changes in the gene expression profile of hepatocytes with BBR treatment under BSA and OA conditions. Results: BBR significantly increased the intracellular TAG content in primary hepatocytes treated with OA, while no significant increase was observed in the BSA treatment group. Bodipy staining experiments also confirmed that BBR led to an increase in the number and size of lipid droplets under OA treatment. Transcriptomic data revealed that under both BSA and OA conditions, BBR upregulated the expression of a large number of genes related to lipid synthesis, which were associated with the activation of the PPARγ signaling pathway. Conclusion: BBR promotes the expression of genes involved in lipid synthesis in primary hepatocytes by activating PPARγ, leading to specific hepatic lipid accumulation under high-fat conditions.
2025-01-29 | GSE274374 | GEO
Project description:Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation mechanism accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the downstream pro-inflammatory IL-1β-HIF1a axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions via its effect on succinate dehydrogenase, by inhibiting conversion of succinate to fumarate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1-/- mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, changes in mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages. Experiment 1: mature WT BMDM were treated for 12h with 0.25 mM dimethyl itaconate (DI) or vehicle (Unst) and then stimulated with LPS (E. coli 0111:B4; 100 ng/ml, 4h) (DI+LPS; LPS); Experiment 2: mature Irg1-/- BMDM were stimulated with LPS (E. coli 0111:B4; 100 ng/ml) and murine recombinant IFNg (50 ng/ml) for 24h.
2016-07-01 | E-GEOD-82043 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE30447: Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-regulated in Nonalcoholic Fatty Liver (HepG2 data) GSE30450: Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-regulated in Nonalcoholic Fatty Liver (hepatocytes data) Refer to individual Series
2011-07-07 | E-GEOD-30451 | biostudies-arrayexpress
Project description:This dataset was generated to confirm that +130 and +146 Da adducts observed in LPS-stimulated macrophages were produced by the itaconate metabolite. To this end, model proteins (bovine serum albumin and human KEAP1) were reacted in vitro with itaconate, and the correspondent adducts were analyzed by LC-MSMS
2021-07-22 | PXD019858 | Pride
Project description:Alcoholic liver disease (ALD) encompasses conditions ranging from simple steatosis to cirrhosis and even liver cancer. It has gained significant global attention in recent years. Despite this, effective pharmacological treatments for ALD remain elusive, and the core mechanisms underlying the disease are not yet fully comprehended. S100A16, a newly identified calcium-binding protein, is linked to lipid metabolism. Our research has discovered elevated levels of the S100A16 protein in both serum and liver tissue of ALD patients. A similar surge in hepatic S100A16 expression was noted in a Gao-binge alcohol feeding mouse model. S100a16 knockdown alleviated ethanol-induced liver injury, steatosis and inflammation. Conversely, S100a16 transgenic mice showed aggravating phenomenon. Mechanistically, we identify mesencephalic astrocyte-derived neurotrophic factor (MANF) as a regulated entity downstream of S100a16 deletion. MANF inhibited ER-stress signal transduction induced by alcohol stimulation. Meanwhile, MANF silencing suppressed the inhibition effect of S100a16 knockout on ethanol-induced lipid droplets accumulation in primary hepatocytes. Our data suggested that S100a16 deletion protects mice against alcoholic liver lipid accumulation and inflammation dependent on upregulating MANF and inhibiting ER stress. This offers a potential therapeutic avenue for ALD treatment.
2023-09-26 | GSE243683 | GEO
Project description:Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2, however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing HMGCS2 and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolism pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. To determine the global impact of Foxa1 on human liver gene transcription, microarray expression analyses were performed in human hepatocytes transfected with Ad-Foxa1 or Ad-Control. We used microarrays to detail the global programme of gene expression in human hepatocytes infected with Ad-Foxa1 or control adenovirus (insertless Ad-pACC).
2011-07-07 | E-GEOD-30450 | biostudies-arrayexpress
Project description:Myristic acid, the 14-carbon saturated fatty acid (C14:0), is usually associated with negative consequences for human health, and in particular its consumption is correlated to an increased cardiovascular disease risk. Since it is a little abundant into the cells, its specific properties and functional roles have not been fully described. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. Primary murine hepatocytes were used as a model to investigate the hepatic response to C14:0 in a proteomic approach. C14:0 treatment (250 µM) of primary murine hepatocytes confirmed that myristic acid induces lipid droplet accumulation as shown by cellular imaging and elevated perilipin 2 levels on cellular proteome level. The functionally enriched pathways were involved in protein synthesis, transport and degradation, protein depalmitoylation, unfolded protein response, lipid and cholesterol metabolism, mitophagy in response to depolarization, and cell cell adhesion. Our data provide for the first time quantitative proteomic data regarding C14:0 in primary murine hepatocytes (M1 in present dataset) and contribute to the elucidation of the molecular mechanisms through which this fatty acid can cause adverse health effects.
2022-03-01 | PXD009017 | Pride