ACOT1, ACOT2, and ACOT3 are involved in fatty acid metabolism and Cyp4a10, and Cyp4a14 are involved in the PPAR signaling pathway downregulated significantly after MSCs treatment in WD-induced NASH liver.
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PROVIDER: PRJNA930379 | ENA |
REPOSITORIES: ENA
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Project description:To identify the therapeutic role of hUC-MSCs cell therapy in WD-induced NASH, we established a NASH mouse model.
2024-02-01 | GSE224233 | GEO
Project description:Purpose: Excessive intake of a western diet (WD), characterized by high fat and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms through which dietary changes lead to IBD development remain unknown. Here, we generated a murine model of severe intestinal inflammation triggered by long-term WD consumption, which exhibited markedly elevated taste receptor TAS1R3 expression in inflamed bowel tissues. Thus, we hypothesized that nutrient-induced TAS1R3 modulation is central to regulating intestinal inflammation. We tested our hypothesis by analyzing changes in gene expression profiles and inflammatory cell infiltration in the inflamed bowel tissues of WD-fed Tas1r3-deficient mice. Methods: We carried out RNA-Seq of ileum tissue of wild-type (WT) and taste receptor Tas1r3 knockout (Tas1r3−/−) mice fed a normal diet (ND) or western diet (WD) for 10 weeks using Ion Proton System. Raw RNA-seq reads were split into individual samples based on barcodes and quality controlled using the FASTQC tool. The reads were analyzed with Partek Flow software (Partek, St. Louis, MI, USA) (http://www.partek.com/partekgs). The sequence reads that passed quality filters were analyzed at the transcript isoform level. Results: We confirmed that Tas1r3-deficient mice are protected from WD-induced intestinal inflammation. Consistent with little or no phenotypic change in the ND group, the gene expression profiles from the ND-fed Tas1r3−/− and WT mice were similar, whereas the ileal transcriptome profiles from the WD-fed Tas1r3−/− mice were readily distinguishable from those of WD-fed WT mice. Inflammatory cytokines such as Tnfα and Il1b were highly expressed in WD-fed WT mice, whereas Pparg, Tjp3, and Defa27 were highly expressed in WD-fed Tas1r3−/− mice. Importantly, we confirmed that the absence of TAS1R3 caused a significant reduction in the inflammatory response-related signaling pathway; GSEA plots also revealed that the mTOR signaling pathway was greatly suppressed. Most notably, the PPAR signaling pathway was significantly affected by TAS1R3 absence. GSEA confirmed that genes associated with the PPAR signaling pathway were significantly enriched in the set of DEGs between Tas1r3−/− and WT mice in the WD groups. Conclusion: Our data suggest that, due to its suppressive action on mTOR, TAS1R3 might function as an important regulator of the PPAR-γ signaling pathway in the intestinal tract.
2023-04-19 | GSE190059 | GEO
Project description:PLAAT3 is a phospholipid modifying enzyme predominantly expressed in neural and white adipose tissue (WAT). It is a potential drug target for metabolic syndrome as Plaat3 deficiency in mice protects against diet-induced obesity. We identified seven patients from four unrelated consanguineous families, with homozygous loss-of-function variants in PLAAT3, presenting a severe lipodystrophy syndrome (LS) associated with metabolic complications, as well as neurological features including demyelinating neuropathy and intellectual disability. Multi-omics analysis of mouse Plaat3-/- and patient-derived WAT showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in the signaling of PPAR?, the master regulator of adipocyte differentiation. The present dataset describes the proteomics shotgun analysis of WAT samples from Plaat3-/- and Plaat3-/+ mice. We found that proteins involved in fatty acid metabolic and lipid biosynthetic processes were less abundant in Plaat3-/- WAT, whereas proteins involved in autophagy and catabolism were more abundant. In line with transcriptomics data obtained from mice and human WAT, PPAR? and its coactivators were identified as strong transcriptional regulators within the set of downregulated proteins. Along with validation experiments in PLAAT3-deficient human adipose stem cells, these findings establish PLAAT3 deficiency as a novel hereditary LS with neurological manifestations, caused by a PPAR?-dependent defect in WAT differentiation and function.
2023-08-29 | PXD038815 | Pride
Project description:Inflammatory bowel disease (IBD) is a condition characterized by severe intestinal inflammation and immune cell activation. The severity of the disease can be mitigated by compounds which activate peroxisome proliferator-activated receptor gamma (PPAR gamma), a receptor present widely in tissues involved in IBD pathogenesis. Our objective was to assess the affect of macrophage-specific deficiency of PPAR gamma on peripheral and colonic immune populations and colonic gene expression in experimental IBD. Macrophage-specific PPAR gamma-deficient mice (PPAR gamma flfl Lysozyme M Cre+) and control (PPAR gamma flfl Lysozyme M Cre-) littermates were treated with 2.5% dextran sodium sulfate (DSS) for 7 days. Disease activity was recorded daily and immune cell populations in the blood, spleen, mesenteric lymph nodes (MLN), and lamina propria were examined by flow cytometry. Colonic gene expression was assessed by real time PCR and microarray analyses. Our findings show that macrophage PPAR r-deficiency significantly exacerbates DSS inflammation. CD4+CD25+FoxP3+ regulatory T cells (T-regs) were significantly reduced in Cre+ mice, and MLN macrophages and CD40 expression were enhanced. There were significant differences in the number colonic macrophages between Cre+ and Cre- mice, but those from Cre+ mice expressed more CD40, Ly6C, and TLR-4. PPAR r-deficiency also increased the percent of CD8+ T cells in the lamina propria and enhanced colonic interferon gamma expression. Our findings indicate that macrophage PPAR gamma deficiency augments the severity of DSS colitis by reducing peripheral T-regs and increasing colonic macrophage activation and T cell inflammation.
2011-11-12 | GSE23421 | GEO
Project description:Inflammatory bowel disease (IBD) is a condition characterized by severe intestinal inflammation and immune cell activation. The severity of the disease can be mitigated by compounds which activate peroxisome proliferator-activated receptor gamma (PPAR gamma), a receptor present widely in tissues involved in IBD pathogenesis. Our objective was to assess the affect of macrophage-specific deficiency of PPAR gamma on peripheral and colonic immune populations and colonic gene expression in experimental IBD. Macrophage-specific PPAR gamma-deficient mice (PPAR gamma flfl Lysozyme M Cre+) and control (PPAR gamma flfl Lysozyme M Cre-) littermates were treated with 2.5% dextran sodium sulfate (DSS) for 7 days. Disease activity was recorded daily and immune cell populations in the blood, spleen, mesenteric lymph nodes (MLN), and lamina propria were examined by flow cytometry. Colonic gene expression was assessed by real time PCR and microarray analyses. Our findings show that macrophage PPAR r-deficiency significantly exacerbates DSS inflammation. CD4+CD25+FoxP3+ regulatory T cells (T-regs) were significantly reduced in Cre+ mice, and MLN macrophages and CD40 expression were enhanced. There were significant differences in the number colonic macrophages between Cre+ and Cre- mice, but those from Cre+ mice expressed more CD40, Ly6C, and TLR-4. PPAR r-deficiency also increased the percent of CD8+ T cells in the lamina propria and enhanced colonic interferon gamma expression. Our findings indicate that macrophage PPAR gamma deficiency augments the severity of DSS colitis by reducing peripheral T-regs and increasing colonic macrophage activation and T cell inflammation. RNA from 3 PPAR gamma-deficient mice (PPAR gamma flfl; Lysozyme M Cre+) and 3 control (PPAR gamma flfl; Lysozyme M Cre-) littermates was processed and labeled according to the standard target labeling protocols. The samples were hybridized, stained, and scanned per standard Affymetrix protocols at the Virginia Bioinformatics Institute (VBI) core laboratory on Mouse 430 2.0 expression arrays (Affymetrix Inc., Santa Clara, CA).
2011-11-12 | E-GEOD-23421 | biostudies-arrayexpress
Project description:Genome-wide profiling of PPAR?:RXR and RNA polymerase II reveals temporal activation of distinct metabolic pathways in RXR dimer composition during adipogenesis. Chromatin immunoprecipitation combined with deep sequencing was performed to generate genome-wide maps of peroxisome prolifelator-activated receptor gamma (PPARg) and retinoid X receptor (RXR) binding sites, and RNA polymerase II (RNAPII) occupancy at high resolution throughout adipocyte differentiation of 3T3-L1 cells. The data provides the first positional and temporal map PPAR? and RXR occupancy during adipocyte differentiation at a global scale. The number of PPAR?:RXR shared binding sites is steadily increasing from D0 to D6. At Day6 there are over 5000 high confidence shared PPARy:RXR binding sites. We show that at the early days of differentiation several of these sites bind not only PPAR?:RXR but also other RXR dimers. The data also provides a comprehensive temporal map of RNAPII occupancy at genes throughout 3T3-L1 adipogenesis thereby uncovering groups of similarly regulated genes belonging to glucose and lipid metabolic pathways. The majority of the upregulated but very few downregulated genes have assigned PPAR?:RXR target sites, thereby underscoring the importance of PPAR?:RXR in gene activation during adipogenesis and indicating that a hitherto unrecognized high number of adipocyte genes are directly activated by PPAR?:RXR Examination of PPARg and RXR bindingsites during adipocyte differentiation (day 0 to 6) and association with transcription via RNAPII occupancy.
2008-12-10 | E-GEOD-13511 | biostudies-arrayexpress
Project description:Thomasclavelia ramosa strain:WD-I2 Genome sequencing and assembly
| PRJNA924240 | ENA
Project description:Connectivity mapping of angiotensin-PPAR interactions involved in the amelioration of non-alcoholic steatohepatitis by Telmisartan
| PRJNA495063 | ENA
Project description:BACKGROUND: Peroxisome proliferator-activated receptor g (PPAR g) is a nuclear receptor whose activation has been shown to modulate macrophage and epithelial cell-mediated inflammation. The objective of this study was to use a systems approach for investigating the mechanism by which the deletion of PPAR g in epithelial cells modulates the severity of dextran-sodium sulfate (DSS)-induced colitis, immune cell distribution and global gene expression. RESULTS: The deficiency of PPAR g in epithelial cells does not significantly affect disease activity or body weight but worsens colon histopathlogy. WT mice have greater CD4+IL10+ T cells and fewer MHC II+ macrophages in mesenteric lymph nodes. Global gene expression analysis reveals greater changes after 7 days of DSS challenge (compared to 2 days).
2010-06-21 | GSE20621 | GEO
Project description:2,4-dinitrotoluene (2,4-DNT), a nitroaromatic used in industrial and explosive manufacturing processes, is known to contaminate artillery ranges, demilitarization areas and munitions manufacturing facilities. Previous transcriptomic and lipidomic studies identified energy metabolism as a principle biochemical process affected by 2,4-DNT where up-stream effects on PPAR? signaling were hypothesized as themolecular initiating event for these effects. Here, the validity of this hypothetical adverse outcome pathway (AOP) was assessed by testing the hypothesis that 2,4-DNT-induced perturbations in PPAR? signaling and resultant downstream deficits in energy metabolism, especially from lipids, would result in organism-level impacts on exercise endurance. PPAR? knock-out (-/-) and wild-type (WT) mice were exposed for 14 days to vehicle or 2,4-DNT at a dose (134 mg/kg/day) that did not exhibit overt systemic toxicity. Mice performed an exercise challenge (forced swim) 1 day after the last dose. 2,4-DNT decreased swim times in WT and PPAR? (-/-) mice, but the effect was significantly less in PPAR? (-/-) mice indicating the critical of PPAR? in mediating 2,4-DNT-induced energy metabolism deficits. 2,4-DNT caused down-regulation of transcripts involved in fatty acid metabolism, gluconeogenesis, triacylglycerol catabolism, and the pentose phosphate pathway, and 2,4-DNT treated wild-type mice had decreased serum trigylcerides and increased serum glucose versus 2,4-DNT treated PPAR? (-/-) mice. Our results support the hypothesis that 2,4-DNT perturbs PPAR? signaling as a molecular initiating event therefore impacting energy metabolism, especially lipid metabolism, producing reduced exercise endurance in mice. RNA was isolated from liver tissue of vehicle or 2,4-DNT treated wild-type or PPAR? (-/-) mice (n=6) and RT-PCR performed to analyze genes involved in fatty acid metabolism
2014-06-30 | E-GEOD-50168 | biostudies-arrayexpress