2023
O-linked N-acetylglucosamine modification is essential for physiological adipose expansion induced by high-fat feeding
Nakamoto A, Ohashi N, Sugawara L, Morino K, Ida S, Perry R, Sakuma I, Yanagimachi T, Fujita Y, Ugi S, Kume S, Shulman G, Maegawa H. O-linked N-acetylglucosamine modification is essential for physiological adipose expansion induced by high-fat feeding. AJP Endocrinology And Metabolism 2023, 325: e46-e61. PMID: 37224467, PMCID: PMC10292976, DOI: 10.1152/ajpendo.00263.2022.Peer-Reviewed Original ResearchConceptsFKO miceAdipose tissueBody weight gainPrimary cultured adipocytesAdipose expansionFree fatty acidsInflammatory genesWeight gainFree fatty acid effluxCultured adipocytesDiet-induced obesityHigh-fat dietHigh-fat feedingLess body weightDe novo lipogenesisAdipose tissue physiologyDe novo lipogenesis genesFatty acid effluxWeeks of ageAdipose inflammationGlucose intoleranceRAW 264.7 macrophagesControl miceFatty acidsSevere fibrosis
2022
Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance
Huang Y, Zhou JH, Zhang H, Canfrán-Duque A, Singh AK, Perry RJ, Shulman G, Fernandez-Hernando C, Min W. Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. Journal Of Clinical Investigation 2022, 132 PMID: 35202005, PMCID: PMC9057632, DOI: 10.1172/jci148852.Peer-Reviewed Original ResearchConceptsBrown adipose tissueBAT inflammationInsulin resistanceMitochondrial reactive oxygen speciesReactive oxygen speciesAberrant innate immune responsesDiet-induced insulin resistanceSystematic metabolismDiet-induced obesityNLRP3 inflammasome pathwayWhole-body energy metabolismCGAS/STINGInnate immune responseFatty acid oxidationExcessive mitochondrial reactive oxygen speciesMetabolic benefitsImmune responseInflammasome pathwayAdipose tissueInflammationInhibition reversesLipid uptakeLipid metabolismThioredoxin 2Adaptive thermogenesis
2021
IL-27 signalling promotes adipocyte thermogenesis and energy expenditure
Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, Cheng H, Wen Q, Xu H, Zhu L, Zhang H, Perry RJ, Spadaro O, Yang Y, He S, Chen Y, Wang B, Li G, Liu Z, Yang C, Wu X, Zhou L, Zhou Q, Ju Z, Lu H, Xin Y, Yang X, Wang C, Liu Y, Shulman GI, Dixit VD, Lu L, Yang H, Flavell RA, Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature 2021, 600: 314-318. PMID: 34819664, DOI: 10.1038/s41586-021-04127-5.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsBariatric SurgeryDisease Models, AnimalEnergy MetabolismFemaleHumansInsulin ResistanceInterleukin-27MaleMiceObesityP38 Mitogen-Activated Protein KinasesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaReceptors, InterleukinSignal TransductionThermogenesisUncoupling Protein 1ConceptsIL-27Beige adipose tissueAdipose tissueSerum IL-27Diet-induced obesityBariatric surgeryMetabolic morbidityImmunological factorsInsulin resistanceObesity showTherapeutic administrationMetabolic disordersMouse modelObesityPromising targetEnergy expenditureSignaling promotesThermogenesisBody temperatureMetabolic programsImportant roleTissueCritical roleImmunotherapyMorbidity
2020
A MicroRNA Linking Human Positive Selection and Metabolic Disorders
Wang L, Sinnott-Armstrong N, Wagschal A, Wark AR, Camporez JP, Perry RJ, Ji F, Sohn Y, Oh J, Wu S, Chery J, Moud BN, Saadat A, Dankel SN, Mellgren G, Tallapragada DSP, Strobel SM, Lee MJ, Tewhey R, Sabeti PC, Schaefer A, Petri A, Kauppinen S, Chung RT, Soukas A, Avruch J, Fried SK, Hauner H, Sadreyev RI, Shulman GI, Claussnitzer M, Näär AM. A MicroRNA Linking Human Positive Selection and Metabolic Disorders. Cell 2020, 183: 684-701.e14. PMID: 33058756, PMCID: PMC8092355, DOI: 10.1016/j.cell.2020.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytes, BrownAdiposityAllelesAnimalsCell DifferentiationCell LineCells, CulturedDiet, High-FatEnergy MetabolismEpigenesis, GeneticGenetic LociGlucoseHomeostasisHumansHypertrophyInsulin ResistanceLeptinMaleMammalsMetabolic DiseasesMice, Inbred C57BLMice, ObeseMicroRNAsObesityOligonucleotidesSpecies SpecificityConceptsPositive selectionMiR-128Additional genetic elementsCrucial metabolic regulatorAncient adaptationEvolutionary adaptationGenetic elementsMetabolic regulatorGenetic ablationLociMetabolic maladaptationLactase geneAntisense targetingMetabolic disease modelsThrifty phenotypeDisease modelsDiet-induced obesityMetabolic diseasesAbility of adultsMammalsAdaptationGenesMicroRNAsRegulatorSelection
2019
Hepatic insulin sensitivity is improved in high‐fat diet‐fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis
Edmunds LR, Huckestein BR, Kahn M, Zhang D, Chu Y, Zhang Y, Wendell SG, Shulman GI, Jurczak MJ. Hepatic insulin sensitivity is improved in high‐fat diet‐fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis. Physiological Reports 2019, 7: e14281. PMID: 31724300, PMCID: PMC6854109, DOI: 10.14814/phy2.14281.Peer-Reviewed Original ResearchConceptsPark2 KO miceHepatic insulin sensitivityKO miceInsulin sensitivityInsulin resistanceShort-term HFD feedingDiet-induced hepatic insulin resistanceWhole-body insulin sensitivityPark2 knockout miceImproved hepatic insulin sensitivityDiet-induced obesityHigh-fat dietBioactive lipid speciesTumor necrosis factorHepatic insulin resistanceHepatic AMPK activationNegative energy balanceEndoplasmic reticulum stress responseRegular chowCytokine levelsHFD feedingReduced steatosisChronic HFDInterleukin-6Necrosis factor
2000
Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice
Klaman L, Boss O, Peroni O, Kim J, Martino J, Zabolotny J, Moghal N, Lubkin M, Kim Y, Sharpe A, Stricker-Krongrad A, Shulman G, Neel B, Kahn B. Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice. Molecular And Cellular Biology 2000, 20: 5479-5489. PMID: 10891488, PMCID: PMC85999, DOI: 10.1128/mcb.20.15.5479-5489.2000.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBody WeightCarrier ProteinsEnergy MetabolismFemaleGlucoseGlucose Tolerance TestHomeostasisHyperinsulinismInsulin ResistanceIon ChannelsLeptinMaleMembrane ProteinsMembrane Transport ProteinsMiceMice, Inbred C57BLMice, Mutant StrainsMitochondrial ProteinsMuscle, SkeletalProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesProteinsRNA, MessengerUncoupling Protein 1Uncoupling Protein 2Uncoupling Protein 3ConceptsProtein tyrosine phosphatasePTP-1BMajor protein tyrosine phosphataseProtein tyrosine phosphatase 1BSignal transduction pathwaysTargeted gene disruptionInsulin-stimulated glucose uptakeGene disruptionTransduction pathwaysFat cell massPhosphatase 1BMajor regulatorProtein mRNA expressionCell massNull miceSkeletal muscleDeficient miceGlucose uptakeBasal metabolic rateInsulin actionMetabolic ratePhosphataseFat storesDiet-induced obesityAdipocyte number