2024
1577-P: CIDEB Knockdown Promotes Increased Hepatic Mitochondrial Fat Oxidation and Reverses Hepatic Steatosis and Hepatic Insulin Resistance by the PKCε-Insulin Receptor Kinase Pathway
ZHENG J, NASIRI A, GASPAR R, HUBBARD B, SAKUMA I, MA X, MURRAY S, PERELIS M, BARNES W, SAMUEL V, PETERSEN K, SHULMAN G. 1577-P: CIDEB Knockdown Promotes Increased Hepatic Mitochondrial Fat Oxidation and Reverses Hepatic Steatosis and Hepatic Insulin Resistance by the PKCε-Insulin Receptor Kinase Pathway. Diabetes 2024, 73 DOI: 10.2337/db24-1577-p.Peer-Reviewed Original ResearchReceptor kinase pathwaysMitochondrial fat oxidationHepatic insulin resistanceKinase pathwayExpression of cidebAmeliorated HFD-induced hepatic steatosisHFD-induced hepatic steatosisHFD-induced insulin resistanceSteatotic liver diseasePathogenesis of type 2 diabetesHepatic steatosisCidebHyperinsulinemic-euglycemic clamp studiesHepatic triglyceride accumulationInsulin resistanceReverse hepatic steatosisTriglyceride accumulationHepatic insulin sensitivityInsulin sensitivityPathwayHepatic expressionHigh-fatWhole-body insulin sensitivityLiver diseaseTranslocation
2023
Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling
Zhang L, Pan Q, Zhang L, Xia H, Liao J, Zhang X, Zhao N, Xie Q, Liao M, Tan Y, Li Q, Zhu J, Li L, Fan S, Li J, Zhang C, Cai S, Boyer J, Chai J. Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling. Hepatology 2023, 77: 1866-1881. PMID: 36647589, PMCID: PMC10921919, DOI: 10.1097/hep.0000000000000041.Peer-Reviewed Original ResearchConceptsJAK/STAT3Bile duct ligationInflammatory responseLiver injuryCholestatic patientsTranscription factor 1Duct ligationBile acidsLiver inflammatory responseCholestatic liver injuryHepatic inflammatory responseElevated bile acidsCholic acid dietFactor 1Cholic acid feedingLiver-specific ablationNew therapeutic targetsLiver-specific deletionCholestatic miceHepatic inflammationLiver inflammationInflammatory chemokinesHepatic expressionMouse modelAcid diet
2021
The integration of genetically-regulated transcriptomics and electronic health records highlights a pattern of medical outcomes related to increased hepatic transthyretin expression
Pathak GA, De Lillo A, Wendt FR, De Angelis F, Koller D, Mendoza B, Jacoby D, Miller EJ, Buxbaum JN, Polimanti R. The integration of genetically-regulated transcriptomics and electronic health records highlights a pattern of medical outcomes related to increased hepatic transthyretin expression. Amyloid 2021, 29: 110-119. PMID: 34935565, PMCID: PMC9213571, DOI: 10.1080/13506129.2021.2018678.Peer-Reviewed Original ResearchConceptsGenotype-Tissue Expression (GTEx) projectMulti-tissue analysisElectronic health recordsTTR amyloid formationGenetic regulationExpression projectRNA interferenceTranscriptomic profilesGene expressionExpression informationHepatic expressionHealth outcomesPhenotypic informationAmyloid formationHealth recordsCarpal tunnel syndromeTranscriptionTransthyretin expressionSystemic amyloidosesHepatic transcriptionPathological processesExpressionTunnel syndromeGastrointestinal diseasesSurgical procedures
2019
Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants
Polimanti R, Nuñez YZ, Gelernter J. Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants. Journal Of Clinical Medicine 2019, 8: 269. PMID: 30813263, PMCID: PMC6406512, DOI: 10.3390/jcm8020269.Peer-Reviewed Original Research
2018
Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5–dependent and –independent mechanisms
Treviño-Villarreal J, Reynolds J, Bartelt A, Langston P, MacArthur M, Arduini A, Tosti V, Veronese N, Bertozzi B, Brace L, Mejia P, Trocha K, Kajitani G, Longchamp A, Harputlugil E, Gathungu R, Bird S, Bullock A, Figenshau R, Andriole G, Thompson A, Heeren J, Ozaki C, Kristal B, Fontana L, Mitchell J. Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5–dependent and –independent mechanisms. JCI Insight 2018, 3: e99470. PMID: 30385734, PMCID: PMC6238732, DOI: 10.1172/jci.insight.99470.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoprotein A-VApolipoproteinsCyclic AMP Response Element-Binding ProteinDiet, Protein-RestrictedFemaleHumansHydrolysisHypertriglyceridemiaLipid MetabolismLipoproteins, VLDLLiverMaleMechanistic Target of Rapamycin Complex 1MiceProtein Serine-Threonine KinasesRandomized Controlled Trials as TopicRisk FactorsTriglyceridesConceptsAPOA5 expressionProtein restrictionTG-lowering effectVLDL-TGIntegrated stress responseFatty acid oxidation-related genesHepatic expressionVLDL triglyceride levelsIndependent risk factorRandomized controlled clinical trialVLDL-TG secretionVLDL-TG hydrolysisDietary protein restrictionDiet-induced obese miceOxidation-related genesVLDL particle numberStress responseExpression of fatty acid oxidation-related genesTriglyceride levelsDietary interventionClinical trialsPlasma triglyceridesAxis activityClinical relevanceObese mice
2017
METHIONINE RESTRICTION ALTERS HEPATIC MIRNAS INVOLVED IN METABOLISM IN YOUNG, OBESE, AND AGED MICE
Park M, Cooke D, Plummer J, Ables G, Hens J. METHIONINE RESTRICTION ALTERS HEPATIC MIRNAS INVOLVED IN METABOLISM IN YOUNG, OBESE, AND AGED MICE. Innovation In Aging 2017, 1: 857-857. PMCID: PMC6184731, DOI: 10.1093/geroni/igx004.3084.Peer-Reviewed Original ResearchDIO miceAged miceMethionine restrictionYoung miceNonalcoholic fatty liver diseaseDiet-induced obese miceMiR-33-5pFatty liver conditionFatty liver diseaseDietary methionine restrictionType II diabetesExpression of mRNAAge-associated disordersBile acid transportLiver diseaseLiver functionObese miceLet-7gLiver conditionsMR dietOld miceHepatic expressionTransport of cholesterolBile acidsII diabetesHepatic inositol 1,4,5 trisphosphate receptor type 1 mediates fatty liver
Feriod CN, Oliveira AG, Guerra MT, Nguyen L, Richards KM, Jurczak MJ, Ruan H, Camporez JP, Yang X, Shulman GI, Bennett AM, Nathanson MH, Ehrlich BE. Hepatic inositol 1,4,5 trisphosphate receptor type 1 mediates fatty liver. Hepatology Communications 2017, 1: 23-35. PMID: 28966992, PMCID: PMC5613674, DOI: 10.1002/hep4.1012.Peer-Reviewed Original ResearchLipid droplet formationFatty liverLiver diseaseHuman fatty liver diseaseFatty liver diseaseNon-alcoholic steatohepatitisDegree of steatosisCalcium signalingHuman liver biopsiesReceptor type 1ER calcium releaseType 1 isoformMitochondrial calcium signalingLiver biopsyHepatic triglyceridesCalcium handlingHepatic expressionKnockout miceTrisphosphate receptor type 1Malignant formUS populationCalcium releaseType 1LiverCommon type
2014
The emerging role of oestrogen-related receptor γ as a regulator of energy metabolism
Samuel VT. The emerging role of oestrogen-related receptor γ as a regulator of energy metabolism. Diabetologia 2014, 57: 2440-2443. PMID: 25257097, PMCID: PMC4488899, DOI: 10.1007/s00125-014-3377-7.Peer-Reviewed Original Research
2013
Hepatic SIRT1 Attenuates Hepatic Steatosis and Controls Energy Balance in Mice by Inducing Fibroblast Growth Factor 21
Li Y, Wong K, Giles A, Jiang J, Lee J, Adams A, Kharitonenkov A, Yang Q, Gao B, Guarente L, Zang M. Hepatic SIRT1 Attenuates Hepatic Steatosis and Controls Energy Balance in Mice by Inducing Fibroblast Growth Factor 21. Gastroenterology 2013, 146: 539-549.e7. PMID: 24184811, PMCID: PMC4228483, DOI: 10.1053/j.gastro.2013.10.059.Peer-Reviewed Original ResearchConceptsControl miceLivers of control miceFibroblast growth factor 21White adipose tissueHepatic overexpressionCirculating LevelsExpression of genesHepatic steatosisEnergy expenditureHormone-like regulatorsLKO miceFasted control miceHepatic expressionAbstractText Label="Background &Late-onset obesityAdipose tissueWild-type littermatesFatty acid oxidationNormal chow dietReal-time polymerase chain reaction assayControl energy balanceHormone fibroblast growth factor 21Severe hepatic steatosisFasting-induced steatosisLevels of FGF21
2012
The Role of the Carbohydrate Response Element-Binding Protein in Male Fructose-Fed Rats
Erion DM, Popov V, Hsiao JJ, Vatner D, Mitchell K, Yonemitsu S, Nagai Y, Kahn M, Gillum MP, Dong J, Murray SF, Manchem VP, Bhanot S, Cline GW, Shulman GI, Samuel VT. The Role of the Carbohydrate Response Element-Binding Protein in Male Fructose-Fed Rats. Endocrinology 2012, 154: 36-44. PMID: 23161873, PMCID: PMC3529388, DOI: 10.1210/en.2012-1725.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisResponse element-binding proteinCarbohydrate response element-binding proteinASO treatmentHepatic expressionNovo lipogenesisElement-binding proteinInsulin-stimulated peripheral glucose uptakeNonalcoholic fatty liver diseaseAntisense oligonucleotideMale Sprague-Dawley ratsHepatic de novo lipogenesisFructose-fed groupHepatic insulin responsivenessFatty liver diseaseFructose fed ratsPeripheral glucose uptakeHyperinsulinemic-euglycemic clampHigh-fat dietHepatic lipid contentHepatic triglyceride secretionHepatic insulin sensitivitySprague-Dawley ratsPlasma triglyceride concentrationsPlasma uric acid
2009
Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes
Samuel VT, Beddow SA, Iwasaki T, Zhang XM, Chu X, Still CD, Gerhard GS, Shulman GI. Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 12121-12126. PMID: 19587243, PMCID: PMC2707270, DOI: 10.1073/pnas.0812547106.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsDiabetes Mellitus, Type 2Dietary FatsFastingFeeding BehaviorFemaleGene Expression Regulation, EnzymologicGluconeogenesisGlucose-6-PhosphataseHumansHyperglycemiaHyperinsulinismInsulin Infusion SystemsLiverMaleMiddle AgedPhosphoenolpyruvate Carboxykinase (ATP)RatsRats, Sprague-DawleyStreptozocinConceptsHigh-fat feedingEndogenous glucose productionHFF ratsExpression of PEPCKHepatic expressionType 2 diabetes mellitusBeta-cell compensationBeta-cell responseFirst rat modelPortal vein infusionLiver biopsy samplesHigher plasma glucosePhosphoenolpyruvate carboxykinaseBariatric surgeryT2DM patientsDiabetes mellitusInsulin resistancePlasma insulinPlasma glucosePortal infusionRat modelRodent modelsVein infusionHyperglycemiaKey gluconeogenic enzymes
2002
The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes
Hines R, McCarver D. The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes. Journal Of Pharmacology And Experimental Therapeutics 2002, 300: 355-360. PMID: 11805191, DOI: 10.1124/jpet.300.2.355.Peer-Reviewed Original ResearchThe Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms
McCarver D, Hines R. The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms. Journal Of Pharmacology And Experimental Therapeutics 2002, 300: 361-366. PMID: 11805192, DOI: 10.1124/jpet.300.2.361.Peer-Reviewed Original ResearchConceptsDrug-metabolizing enzyme expressionFetal liverN-acetyltransferase 1 (NAT1) activitiesPhase II conjugation enzymeHuman drug metabolizing enzymesEnzyme expressionDrug metabolizing enzymesPaucity of dataPhase II enzymesCCAAT/enhancer binding protein (C/EBP) familyHepatocyte nuclear factorSecond trimesterAdrenal glandHepatic expressionPostnatal changesNAT1 expressionFetal expressionNuclear factorUDP-glucuronosyltransferasePhase ILiverSulfotransferase isoformsRelated factorsIsoform expression patternLimited data
2001
Cellular localization and up‐regulation of multidrug resistance–associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver
Soroka C, Lee J, Azzaroli F, Boyer J. Cellular localization and up‐regulation of multidrug resistance–associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 2001, 33: 783-791. PMID: 11283840, DOI: 10.1053/jhep.2001.23501.Peer-Reviewed Original ResearchConceptsObstructive cholestasisMultidrug resistance-associated protein 3Bile duct-ligated animalsMultidrug resistanceToxic bile acidsModel of cholestasisDuct-ligated animalsExpression of MRP3Intensity of stainingHepatocytes of liverWestern blot analysisBile ductHepatic expressionCentral veinCholestasisMRP3 expressionNormal liverBile acidsPericentral regionsIndirect immunofluorescenceProtein 3Days postligationMRP3Mrp2 proteinLiver
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