2023
Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndothelial CellsFibrosisHepatocytesHumansKupffer CellsLiverMiceNon-alcoholic Fatty Liver DiseaseConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCellsRising NAFLD and metabolic severity during the Sars‐CoV‐2 pandemic among children with obesity in the United States
Slusher A, Hu P, Samuels S, Tokoglu F, Lat J, Li Z, Alguard M, Strober J, Vatner D, Shabanova V, Caprio S. Rising NAFLD and metabolic severity during the Sars‐CoV‐2 pandemic among children with obesity in the United States. Obesity 2023, 31: 1383-1391. PMID: 36694381, PMCID: PMC10186584, DOI: 10.1002/oby.23728.Peer-Reviewed Original ResearchMeSH KeywordsCOVID-19HumansLiverMagnetic Resonance ImagingNon-alcoholic Fatty Liver DiseaseObesityPandemicsSARS-CoV-2United StatesConceptsNonalcoholic fatty liver diseaseOral glucose tolerance testGlucose tolerance testProton density fat fractionLiver diseaseSars-Cov-2 pandemicTolerance testSeverity of NAFLDMagnetic resonance imaging-derived proton density fat fractionFrequency-matched control groupIntrahepatic fat contentCommon liver diseaseFatty liver diseasePediatric obesity clinicVisceral adipose tissueGlobal pandemicNAFLD prevalenceObesity clinicMetabolic severityInsulin secretionAdipose tissueControl groupObesityPatient careHealth differences
2020
Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease.
Ter Horst KW, Vatner DF, Zhang D, Cline GW, Ackermans MT, Nederveen AJ, Verheij J, Demirkiran A, van Wagensveld BA, Dallinga-Thie GM, Nieuwdorp M, Romijn JA, Shulman GI, Serlie MJ. Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease. Diabetes Care 2020, 44: 489-498. PMID: 33293347, PMCID: PMC7818337, DOI: 10.2337/dc20-1644.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes Mellitus, Type 2HumansInsulinInsulin ResistanceLipogenesisLiverNon-alcoholic Fatty Liver DiseaseConceptsNonalcoholic fatty liver diseaseDe novo lipogenesisFatty liver diseaseBariatric surgeryLiver diseaseImpaired insulin-mediated suppressionGlucose productionHepatic de novo lipogenesisPeripheral glucose metabolismHyperinsulinemic-euglycemic clampType 2 diabetesInsulin-mediated suppressionInsulin-resistant subjectsHepatic insulin resistanceLiver biopsy samplesSuppress glucose productionLipogenic transcription factorsInsulin-mediated regulationObese subjectsInsulin resistanceAcute increaseNovo lipogenesisGlucose metabolismBiopsy samplesParadoxical increase
2018
Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents
Vatner DF, Goedeke L, Camporez JG, Lyu K, Nasiri AR, Zhang D, Bhanot S, Murray SF, Still CD, Gerhard GS, Shulman GI, Samuel VT. Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents. Diabetologia 2018, 61: 1435-1446. PMID: 29497783, PMCID: PMC5940564, DOI: 10.1007/s00125-018-4579-1.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAngiopoietin-Like Protein 8Angiopoietin-like ProteinsAnimalsBody CompositionCalorimetry, IndirectDiet, High-FatGlucose Tolerance TestInsulin ResistanceLipid MetabolismMaleMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseOligonucleotides, AntisensePeptide HormonesRatsRats, Sprague-DawleyConceptsHepatic insulin resistanceAdipose tissue lipoprotein lipaseInsulin resistanceEctopic lipid accumulationTissue lipoprotein lipaseAdipose tissueLipid uptakeTolerance testFed miceNon-alcoholic fatty liver diseaseAntisense oligonucleotideMixed meal tolerance testLipoprotein lipaseLipid accumulationDiet-induced NAFLDBariatric surgery patientsFatty liver diseaseHyperinsulinaemic euglycaemic clampMeal tolerance testSecond-generation antisense oligonucleotideAmeliorate insulin resistanceType 2 diabetesLipid-induced hepatic insulin resistanceLipoprotein lipase inhibitorWhite adipose tissue
2017
Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans
Horst K, Gilijamse PW, Versteeg RI, Ackermans MT, Nederveen AJ, la Fleur SE, Romijn JA, Nieuwdorp M, Zhang D, Samuel VT, Vatner DF, Petersen KF, Shulman GI, Serlie MJ. Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans. Cell Reports 2017, 19: 1997-2004. PMID: 28591572, PMCID: PMC5469939, DOI: 10.1016/j.celrep.2017.05.035.Peer-Reviewed Original ResearchMeSH KeywordsCeramidesDiglyceridesEnzyme ActivationFemaleHumansInsulin ResistanceMaleNon-alcoholic Fatty Liver DiseaseProtein Kinase C-epsilonProtein TransportConceptsHepatic insulin resistanceInsulin resistanceHepatic steatosisObese subjectsPKCε activationTissue-specific insulin sensitivityHepatic ceramide contentPeripheral insulin resistanceHepatic lipid accumulationPathogenesis of NAFLDLiver biopsyIntrahepatic triglyceridesLiver fatInsulin sensitivityAdipose tissueTranslational evidenceSteatosisLipid accumulationCeramide contentPKCε translocationSubjectsMolecular mechanismsDiacylglycerol contentHumansActivation