Search results for "Peroxisome proliferator"

showing 10 items of 132 documents

Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.

2020

Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…

Research paperTGFβ Transforming Growth Factor BetaIntracellular SpaceCRISPR Clustered Regularly Interspaced Short Palindromic RepeatshHEPS Human HepatocytesMice0302 clinical medicineLPIAT1DAG Diacylglyceroli.p. Intraperitonealmedia_commonFatty AcidsGeneral Medicine3. Good health030220 oncology & carcinogenesisHOMA-IR homeostasis Model Assessment of Insulin ResistanceMPO morpholinolcsh:Medicine (General)medicine.medical_specialtyPE Phosphatidyl-EthanolamineNashGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesTNFα tumor Necrosis Factor AlphaLDL Low Density LipoproteinsHyperinsulinismNAFLDSD Standard Dietmedia_common.cataloged_instanceHumansCPT1 Carnitine Palmitoyltransferase IPhosphatidylinositolGene SilencingEuropean unionVLDL Very Low Density Lipoproteinlcsh:RhHSC Human Hepatic Stellate Cellsmedicine.diseaseLipid MetabolismOA Oleic AcidCI Confidence IntervalMboat7 Membrane bound O-acyltransferase domain containing 7MCD methionine choline deficient diet030104 developmental biologyEndocrinologychemistryCDP Cytidine-DiphosphateFOXO1 Forkhead Box protein O1NAFLD nonalcoholic fatty liver diseaseSteatohepatitisBMI Body Mass IndexCL CardiolipinAcyltransferases0301 basic medicineAlcoholic liver diseaseCXCL10 C-X-C Motif Chemokine 10lcsh:Medicinechemistry.chemical_compoundNon-alcoholic Fatty Liver DiseaseIFG Impaired Fasting GlucoseAPOB Apolipoprotein BNonalcoholic fatty liver diseasePIP Phosphatidyl-Inositol-PhosphateSteatohepatitisqRT-PCR quantitative Real Time Polymerase Chain ReactionMice Knockoutlcsh:R5-920ORO Oil Red O StainingPI PhosphatidylinositolFatty liverTM6SF2 Transmembrane 6 Superfamily Member 2PhospholipidTAG TriglyceridesNASH Nonalcoholic SteatohepatitisLipogenesisLPA Lyso-Phosphatidic AcidPhosphatidylinositolSignal TransductionPS Phosphatidyl-SerinePA Palmitic AcidALD alcoholic liver diseasePC Phosphatidylcholinei.v. IntravenousFATP1 Fatty Acid Transport Protein 1Models BiologicalInternal medicinemedicineAnimalsNonalcoholic fatty liver diseasePPARα Peroxisome Proliferator-Activated Receptor alphaObesityG3P Glyceraldehyde-3-PhosphateSREBP1c Sterol Regulatory Element-Binding Protein 1HDL High Density Lipoproteinsbusiness.industryPI3K Phosphatidylinositol 3 KinaseMembrane ProteinsNHEJ Non-Homologues End JoiningPNPLA3 Patatin-like Phospholipase Domain-containing-3MTTP Microsomal Triglyceride Transfer ProteinLPIAT1 Lysophosphatidylinositol Acyltransferase 1TMC4 Transmembrane Channel-Like 4Disease Models AnimalGene Expression RegulationHepatocytesFOXA2 Forkhead Box A2mTOR mammalian target of RapamycinSteatosisInsulin ResistancebusinessPG Phosphatidyl-GlycerolFABP1 Fatty Acid-Binding Protein 1 FAS Fatty Acid SynthaseT2DM Type 2 Diabetes MellitusEBioMedicine
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The peroxisome proliferator response element (PPRE) present at positions -681/-669 in the rat liver 3-ketoacyl-CoA thiolase B gene functionally inter…

2000

Although previous data showed that the putative thiolase B PPRE located at -681/-669 bind the PPARalpha-RXRalpha heterodimer in vitro (Kliewer et al. (1992) Nature 358, 771-774), there is no evidence about the functional role of this element. By gel mobility-shift assay, we found an interaction of this PPRE with not only PPARalpha but also with HNF-4. By transfection of cells with the putative PPRE-driven luciferase reporter vector and PPARalpha, we found no significant activation of the luciferase gene expression, in contrast to the case with reporter expression driven by the PPRE of the peroxisomal bifunctional enzyme. On the other hand, HNF-4 activated the luciferase gene expression driv…

Response elementBiophysicsReceptors Cytoplasmic and NuclearBiologyTransfectionBiochemistryDNA-binding proteinPeroxisomal Bifunctional EnzymeGenes ReporterGene expressionAnimalsMolecular BiologyGeneDNA PrimersBase SequenceThiolaseCell BiologyTransfectionDNAAcetyl-CoA C-AcyltransferasePhosphoproteinsMolecular biologyRatsDNA-Binding ProteinsHepatocyte nuclear factor 4Hepatocyte Nuclear Factor 4LiverCOS CellsPeroxisome ProliferatorsTranscription FactorsBiochemical and biophysical research communications
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PGC-1α signaling coordinates susceptibility to metabolic and oxidative injury in the inner retina.

2013

Retinal ganglion cells (RGCs), used as a common model of central nervous system injury, are particularly vulnerable to metabolic and oxidative damage. However, molecular mechanisms underlying this sensitivity have not been determined in vivo . PGC-1α (encoded by PPARGC1A ) regulates adaptive metabolism and oxidative stress responses in a tissue- and cell-specific manner. Aberrant PGC-1α signaling is implicated in neurodegeneration, but the mechanism underlying its role in central nervous system injury remains unclear. We provide evidence from a mouse model that PGC-1α expression and activity are induced in adult retina in response to metabolic and oxidative challenge. Deletion of Ppargc1a d…

Retinal Ganglion CellsCentral nervous systemOxidative phosphorylationBiologymedicine.disease_causeRetinal ganglionPathology and Forensic MedicineMicemedicineIn Situ Nick-End LabelingAnimalsHumansIn Situ HybridizationMice KnockoutRetinaReverse Transcriptase Polymerase Chain ReactionNeurodegenerationAnatomyTFAMmedicine.diseaseImmunohistochemistryPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaCell biologyOxidative Stressmedicine.anatomical_structureAstrocytessense organsOxidative stressAstrocyteSignal TransductionTranscription FactorsThe American journal of pathology
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An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes.

2022

Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists (“glitazones”) are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that po…

RosiglitazoneDiabetes Mellitus Type 2PioglitazonePeroxisome Proliferator-Activated ReceptorsHumansHypoglycemic AgentsThiazolidinedionescardiovascular risk metabolic syndrome pioglitazone type 2 diabetes mellitusGeneral MedicineMedicina (Kaunas, Lithuania)
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Socs3 induction by PPARγ restrains cancer-promoting inflammation

2013

The presence of proinflammatory cytokines in the tumor microenvironment can support further growth of established cancers. Docosahexaenoic acid (DHA), a peroxisome proliferator-activated receptor-gamma (PPARγ) ligand, has been shown to suppress inflammation and limit tumor progression in vivo. Are the anticancer properties of DHA relying on its ability to prevent inflammation? If so, what are the molecular links between the anti-inflammatory properties of DHA and its anticancer effects? DHA is an n-3 polyinsaturated fatty acid mainly found in fish oil that was shown to contribute to inflammation resolution by preventing the release of proinflammatory mediators in vivo.1 DHA has also been as…

STAT3 Transcription FactorDocosahexaenoic AcidsCellular differentiationPeroxisome proliferator-activated receptorInflammationSuppressor of Cytokine Signaling ProteinsBiologyEditorials: Cell Cycle FeaturesProinflammatory cytokineMicemedicineAnimalsHumansPhosphorylationPromoter Regions GeneticMolecular BiologyCells Culturedchemistry.chemical_classificationInflammationTumor microenvironmentInterleukin-17TroglitazoneCell DifferentiationCell BiologyPPAR gammaCell Transformation NeoplasticchemistryGene Expression RegulationSuppressor of Cytokine Signaling 3 ProteinImmunologyCancer cellCancer researchTh17 CellsInterleukin 17medicine.symptomDevelopmental Biologymedicine.drugProtein BindingSignal TransductionCell Cycle
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Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expres…

2010

Steatosis is the first step in the development of non-alcoholic fatty liver disease (NAFLD). However, the mechanisms involved in its pathogenesis are not fully understood. Many nuclear receptors (NRs) involved in energy homeostasis and biotransformation constitute a network connecting fatty acids, cholesterol and xenobiotic metabolisms; therefore, multiple NRs and their ligands may play a prominent role in liver fat metabolism and accumulation. In this study we have attempted to gain insight into the relevance of the NR superfamily in NAFLD by investigating the steatogenic potential of 76 different NR ligands in fatty acid overloaded human hepatocytes and hepatoma cells. Moreover, we have d…

Selective Estrogen Receptor ModulatorsIndolesPeroxisome proliferator-activated receptorReceptors Cytoplasmic and NuclearBiologyRetinoid X receptorPhloroglucinolToxicologyLigandsCalcitriol receptorBridged Bicyclo CompoundsPregnenedionesmedicineHumansLiver X receptorVitamin ACells CulturedCalcifediolchemistry.chemical_classificationPregnane X receptorAndrostenolsTerpenesFatty liverFatty acidGeneral MedicineHep G2 Cellsmedicine.diseaseFarnesolFatty LiverPPAR gammaTamoxifenCholesterolNuclear receptorchemistryBiochemistryHepatocytesChemico-biological interactions
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Ciprofibrate stimulates protein kinase C-dependent phosphorylation of an 85 kDa protein in rat Fao hepatic derived cells

2000

The effect of ciprofibrate on early events of signal transduction was previously studied in Fao cells. Protein kinase C (PKC) assays performed on permeabilized cells showed a more than two-fold increase in PKC activity in cells treated for 24 h with 500 microM ciprofibrate. To show the subsequent effect of this increase on protein phosphorylation, the in vitro phosphorylation on particulate fractions obtained from Fao cells was studied. Among several modifications, the phosphorylation of protein(s) with an apparent molecular mass of 85 kDa was investigated. This modification appeared in the first 24 h of treatment with 500 microM ciprofibrate. It was shown to occur on Ser/Thr residue(s). It…

ThreonineBiochemistryCell LineSubstrate SpecificityMAP2K7Clofibric AcidSerinemedicineAnimalsProtein phosphorylationPhosphorylationProtein Kinase CProtein kinase CbiologyKinaseCyclin-dependent kinase 2Fibric AcidsGeneral MedicinePhosphoproteinsMolecular biologyRatsMolecular WeightLiverBiochemistrybiology.proteinPhosphorylationPeroxisome ProliferatorsCiprofibrateSignal transductionmedicine.drugBiochimie
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Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4α upregulation in primary human hepatocytes

2013

Abstract Background Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Its liver-specific expression in hepatocytes is strongly controlled by hepatocyte nuclear factor-4α (HNF4α). HNF4α expression and transcriptional activity have been demonstrated to be augmented by glucocorticoid receptor (GR) in human hepatocytes and rodent livers. Methods It was examined whether GR activation indirectly induces OCT1 gene expression via HNF4α up-regulation in primary human hepatocytes.We also examined which other transcription factors are involved in OCT1 gene expression and whether they are regulated by dexa…

Time FactorsPrimary Cell CultureTransfectionDexamethasoneReceptors GlucocorticoidGlucocorticoid receptorTransduction GeneticEnhancer bindingCoactivatorGene expressionHumansRNA MessengerGlucocorticoidsTranscription factorPharmacologyRegulation of gene expressionChemistryCCAAT-Enhancer-Binding Protein-betaOrganic Cation Transporter 1Hep G2 CellsGeneral MedicineTransfectionPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaMolecular biologyUp-RegulationHepatocyte Nuclear Factor 4Cell cultureHepatocytesTranscription FactorsPharmacological Reports
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A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability

2017

AbstractProteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed…

Transcriptional Activation0301 basic medicinenatural productTime FactorsPeroxisome proliferator-activated receptorApoptosisLigandsPartial agonistArticleRosiglitazonePPAR_gammaJurkat Cells03 medical and health sciencesTransactivation0302 clinical medicineproteomicsHumansBinding siteReceptorMode of actionPI3K/AKT/mTOR pathwayCell Proliferationchemistry.chemical_classificationBinding SitesMultidisciplinaryProtein StabilityProtein Proliferator-Activated-Receptor PPARs Ligand-Binding Domain Chemical Proteomics Accurate Docking Pi3k/Akt Pathway Drug Discovery Anticancer compoundsReproducibility of ResultsEstersSurface Plasmon ResonanceMolecular Docking SimulationPPAR gammaKineticsHEK293 Cells030104 developmental biologychemistryBiochemistryDocking (molecular)030220 oncology & carcinogenesisThermodynamicsThiazolidinedionesproteomics PPAR_gamma natural productDiterpenes KauraneHT29 CellsScientific Reports
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Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes

2001

The enzymes required for the beta-oxidation of fatty acyl-CoA are present in peroxisomes and mitochondria. Administration of hypolipidaemic compounds such as clofibrate to rodents leads to an increase in the volume and density of peroxisomes in liver cells. These proliferators also induce simultaneously the expression of genes encoding acyl-CoA oxidase, enoyl-CoA hydratase-hydroxyacyl-CoA dehydrogenase (multifunctional enzyme) and thiolase (3-ketoacyl-CoA thiolase). All these enzymes are responsible for long-chain and very-long-chain fatty acid beta-oxidation in peroxisomes. Similar results were observed when rat hepatocytes, or liver-derived cell lines, were cultured with a peroxisome prol…

Transcriptional ActivationGuinea PigsResponse elementReceptors Cytoplasmic and NuclearBiologyBiochemistryGene Expression Regulation EnzymologicMicechemistry.chemical_compoundPeroxisomesAnimalsAcetyl-CoA C-AcetyltransferasePhosphorylationTranscription factorProtein Kinase Cchemistry.chemical_classificationFatty acid metabolismThiolaseFatty AcidsFatty acidPeroxisomeRatsLiverchemistryBiochemistryAcetyl-CoA C-acetyltransferasePeroxisome proliferator-activated receptor alphaSignal TransductionTranscription FactorsBiochemical Society Transactions
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