Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA150831 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism.
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Project description:Hepatic metabolic derangements are key components in the development of fatty liver, insulin resistance, and atherosclerosis. SIRT1, a NAD+-dependent protein deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. Here we demonstrate that hepatic SIRT1 regulates fatty acid metabolism by positively regulating PPAR-alpha. Hepatocyte-specific deletion of SIRT1 impairs PPAR-alpha signaling and decreased fatty acid beta-oxidation in the liver. When challenged with a high-fat diet, liver-specific SIRT1 knockout mice develop hepatic steatosis, hepatic inflammation, and endoplasmic reticulum stress. Taken together, our data indicate that SIRT1 plays a vital role in the regulation of hepatic lipid homeostasis.
2009-04-07 | GSE14921 | GEO
Project description:Regulation between the fed and fasted state in mammals is partially controlled by peroxisome proliferator activated receptor-alpha (PPAR-alpha). Expression of the receptor is high in liver, heart and skeletal muscle, but decreases with age. A combined 1H NMR spectroscopy and GC-MS metabolomic approach has been used to examine metabolism in liver, heart, skeletal muscle and adipose tissue in PPAR-alpha null mice and wild type controls during ageing between 3-13 months. For the PPAR-alpha-null mouse multivariate statistics highlighted hepatic steatosis, reductions in the concentrations of glucose and glycogen in both liver and muscle tissue, and profound changes in lipid metabolism in each tissue, reflecting known expression targets of the PPAR-alpha receptor. Hepatic glycogen and glucose also decreased with age for both genotypes. These findings indicate the development of age related hepatic steatosis in the PPAR-alpha-null mouse, with the normal metabolic changes associated with ageing exacerbating changes associated with genotype. Furthermore, the combined metabolomic and multivariate statistics approach provides a robust method for examining the interaction between age and genotype. </p> The GC-MS assay for this study can be found in the MetaboLights study MTBLS314.
2018-10-11 | MTBLS261 | MetaboLights
Project description:This study systematically investigated the impact of ACE2 knockout (ACE2KO) on hepatic metabolic homeostasis and its molecular mechanisms, using integrated transcriptomic, proteomic, and metabolomic profiling. ACE2 deficiency exacerbates hepatic lipid accumulation, as evidenced by elevated total cholesterol and triglyceride levels, while disrupting the renin-angiotensin system equilibrium via increased angiotensin II (Ang II) and reduced Ang-(1-7). Histopathological analysis revealed hepatocyte edema, vacuolar degeneration, and inflammatory infiltration in the ACE2KO mice. Multi-omics integration uncovered systemic metabolic dysregulation: transcriptomics identified 1,004 differentially expressed genes (DEGs), including lipid metabolism regulators (Scd1, Fabp1) and circadian rhythm modulators (Arntl, Cry1), 191 differentially expressed proteins (DEPs) associated with interferon signaling activation (Oas1a, Rsad2) and lipid synthesis suppression (Scd1, Fasn), and metabolomics highlighted 193 differential metabolites (DEMs) indicative of bile acid dysregulation, glutathione redox imbalance, and amino acid metabolism anomalies. Cross-omics analysis indicated that the PPAR signaling pathway is a central regulatory hub driving lipid metabolic reprogramming and oxidative stress amplification. Furthermore, ACE2 deletion disrupted cytochrome P450-mediated detoxification and glutathione metabolism, thereby establishing a self-reinforcing oxidative injury cycle. These findings comprehensively delineate ACE2’s multifaceted role in hepatic metabolic homeostasis and provide mechanistic insights into and therapeutic targets for ACE2-associated liver diseases.
2025-06-23 | PXD063359 | Pride
Project description:HFPO-DA (ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate; CASRN 62037-80-3; trade name “GenX”) is an alternative to environmentally persistent per- and poly-fluorinated alkyl substances (PFAS). The liver is the primary target of toxicity for HFPO-DA in rodents and previous examination of hepatic transcriptomic responses in mice following oral exposure to HFPO-DA for 90 days showed induction of peroxisome proliferator-activated receptor (PPAR) signaling pathways, predominantly by PPAR alpha, as well as increased gene expression of both peroxisomal and mitochondrial fatty acid metabolism. To further investigate the mechanism of liver toxicity, transcriptomic analysis was conducted on liver tissue from mice orally exposed to 0, 0.1, 0.5 or 5 mg/kg-bw/day HFPO-DA in a reproduction/developmental toxicity study. Hepatic gene expression changes were consistent with the previous 90-day mouse study, demonstrating activation of the PPAR alpha signaling pathway. Peroxisomal and mitochondrial fatty acid beta-oxidation gene sets were enriched at lower HFPO-DA concentrations, and complement cascade, cell cycle and apoptosis related gene sets were enriched at higher HFPO-DA concentrations. These results support the reported histopathological findings in livers of mice from this study and indicate that these effects are mediated through rodent-specific PPAR alpha signaling mechanisms.
2022-06-08 | GSE202302 | GEO
Project description:Characterization of Peroxisome Proliferator-Activated Receptor alpha (PPAR(alpha)) - Independent Effects of PPAR(alpha) Activators in the Rodent Liver: Di-(2-ethylhexyl) phthalate Activates the Constitutive Activated Receptor data files in this series indicate the involvement of PPAR(alpha) and CAR regulatory pathway after DEHP treatment. Keywords: gene expression/microarray
2009-10-20 | GSE18564 | GEO
Project description:To test whether NDGA attenuate dyslipidemia and hepatic steatosis by enhancing fatty acid oxidation through activation of PPAR-α. Using wild type (WT, C57BL/6) fed with chow diet as control, WT mice were either fed with high-fat diet or high-fat diet with NDGA (2.5g/kg food); ob/ob mice were fed with either chow or chow with NDGA (2.5 g/kg food), and maintained on the respective diets for 16 weeks. The expression of lipid metabolism related genes in the liver of these mice were analyzed using Phalanx GPL6845 platform (Mouse OneArray V1). Together with other biochemical/physiological data, our results suggest that the beneficial actions of NDGA on dyslipidemia and hepatic steatosis in ob/ob mice are exerted primarily through enhanced fatty acid oxidation and energy utilization via the activation of PPAR- α receptor activity.
2012-03-30 | GSE35075 | GEO
Project description:We performed MS to analyze the acetylation site of PPAR alpha via PPAR alpha antibody (Cat#GTX101098) . Samples used were mice hepatic cell line AML 12 treated with DMSO or mg149.
2023-10-19 | PXD046231 |
Project description:Aims: To compare the molecular and biologic signatures of a balanced dual peroxisome proliferator-activated receptor-α/γ (PPAR-α/γ) agonist, aleglitazar, with tesaglitazar (a dual PPAR-α/γ agonist) or combination of pioglitazone (PPAR-γ agonist)/fenofibric acid (PPAR-α agonist) in human hepatocytes. Methods and Results: Gene expression microarray profiles were obtained from primary human hepatocytes treated with EC50-aligned low, medium, and high concentrations of the three treatments. A systems-biology approach, Causal Network Modeling, was used to model the data to infer upstream molecular mechanisms that may explain the observed changes in gene expression. Aleglitazar, tesaglitazar and pioglitazone/fenofibric acid, each induced unique transcriptional signatures, despite comparable core PPAR signaling. Although all treatments inferred qualitatively similar PPAR-α signaling, aleglitazar was inferred to have greater effects on high- and low-density lipoprotein cholesterol levels than tesaglitazar and pioglitazone/fenofibric acid, due to greater number of gene expression changes in pathways related to HDL and LDL metabolism. Distinct transcriptional and biologic signatures were also inferred for stress responses, which appeared to be less affected by aleglitazar than the comparators. In particular, pioglitazone/fenofibric acid was inferred to increase NFE2L2 activity, a key component of the stress response pathway, while aleglitazar had no significant effect. All treatments were inferred to decrease proliferative signaling. Conclusions: Aleglitazar induces transcriptional signatures related to lipid parameters and stress responses that are unique from other dual PPAR-α/γ treatments. This may underlie observed favorable changes in lipid profiles in animal and clinical studies with aleglitazar and suggests a differentiated gene profile compared with other dual PPAR-α/γ agonist treatments.
2011-10-22 | GSE33152 | GEO
Project description:We aimed to characterize changes in hepatic miRNA expression associated with inhibition of PPAR-α signaling.
2017-12-20 | GSE108267 | GEO