2022
Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity
Anam AK, Cooke KM, Dratver MB, O'Bryan JV, Perley LE, Guller SM, Hwang JJ, Taylor HS, Goedeke L, Kliman HJ, Vatner DF, Flannery CA. Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity. Molecular Metabolism 2022, 64: 101574. PMID: 35970449, PMCID: PMC9440306, DOI: 10.1016/j.molmet.2022.101574.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisFetal adiposityFatty acid uptakeMaternal obesityObese womenNormal weightExcess adiposityVillous explantsInsulin receptorNewborns of mothersNormal-weight womenAcid uptakePlacental villous explantsTranscription factor SREBP-1Insulin-like growth factor 2Effect of insulinFatty acid oxidationPlacental triglyceridesPlacental responsesElevated triglyceridesMaternal hyperglycemiaWeight womenGrowth factor 2Diabetes riskPlacental metabolism
2018
Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis
Aryal B, Singh AK, Zhang X, Varela L, Rotllan N, Goedeke L, Chaube B, Camporez JP, Vatner DF, Horvath TL, Shulman GI, Suárez Y, Fernández-Hernando C. Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI Insight 2018, 3: e97918. PMID: 29563332, PMCID: PMC5926923, DOI: 10.1172/jci.insight.97918.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAllelesAngiopoietin-Like Protein 4AnimalsAtherosclerosisBody WeightChemokinesCytokinesDiet, High-FatDiet, WesternFatty AcidsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGlucoseInsulinIntegrasesIntercellular Signaling Peptides and ProteinsLipid MetabolismLipoprotein LipaseLipoproteinsLiverMaleMiceMice, Inbred C57BLMice, KnockoutMusclesObesityProprotein Convertase 9TriglyceridesConceptsAngiopoietin-like protein 4High-fat dietEctopic lipid depositionLipid depositionGlucose toleranceLipoprotein lipaseShort-term high-fat dietSevere metabolic abnormalitiesProgression of atherosclerosisMajor risk factorTriacylglycerol-rich lipoproteinsFatty acid uptakeAdipose tissue resultsProatherogenic lipoproteinsCardiometabolic diseasesMetabolic abnormalitiesKO miceRisk factorsWhole body lipidMetabolic disordersGlucose metabolismLPL activityAdipose tissueGenetic ablationRapid clearanceAngptl8 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
Regulation of hepatic glucose metabolism in health and disease
Petersen MC, Vatner DF, Shulman GI. Regulation of hepatic glucose metabolism in health and disease. Nature Reviews Endocrinology 2017, 13: 572-587. PMID: 28731034, PMCID: PMC5777172, DOI: 10.1038/nrendo.2017.80.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHepatic glucose metabolismGlucose metabolismAdipose lipolysisHepatic insulin resistanceNonesterified fatty acidsGlucose metabolism regulationHepatic glycogen metabolismInsulin resistancePharmacological interventionsPathophysiological processesHepatic gluconeogenesisMajor direct effectAcute regulationGlycogen metabolismInsulinMetabolismLipolysisMetabolism regulationFatty acidsProtein phosphorylationTranscriptional mechanismsAnabolic fluxesDirect effectSubstrate availabilityHyperglucagonaemiaHepatic 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 ResearchConceptsHepatic 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