2025
Protein Tyrosine Phosphatases in Metabolism: A New Frontier for Therapeutics
Bennett A, Tiganis T. Protein Tyrosine Phosphatases in Metabolism: A New Frontier for Therapeutics. Annual Review Of Physiology 2025, 87: 301-324. PMID: 39531392, DOI: 10.1146/annurev-physiol-022724-105540.Peer-Reviewed Original ResearchProtein tyrosine phosphataseFunction of protein tyrosine phosphatasesActions of protein tyrosine kinasesTyrosine phosphorylation-dependent signalingTyrosine phosphataseType 2 diabetesPhosphorylation-dependent signalingPathophysiology of metabolic diseasesPrevalence of chronic metabolic disordersProtein tyrosine kinasesMetabolic disordersChronic metabolic disorderMetabolic homeostasisTyrosine kinaseIncreased prevalencePharmaceutical strategiesMetabolic diseasesGlucose metabolismMetabolismProteinBody weightObesityPhosphataseComplex interplayDisorders
2024
Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis
Wang H, Du Y, Huang S, Sun X, Ye Y, Sun H, Chu X, Shan X, Yuan Y, Shen L, Bi Y. Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis. Nature Communications 2024, 15: 4827. PMID: 38844451, PMCID: PMC11156882, DOI: 10.1038/s41467-024-48914-w.Peer-Reviewed Original ResearchConceptsAdipose progenitor cellsT2D patientsProgenitor cellsDiphtheria toxin A expressionHeterogeneous stromal cellsGlycemic disturbancesAdipose tissueInfluence of obesityGlucose homeostasisVisceral adipose tissueHuman visceral adipose tissueImpaired glucose homeostasisType 2 diabetesHunter-killer peptidesRegulating glucose homeostasisSingle-cell analysisAPC functionStromal cellsA expressionMetabolic homeostasisAdipocyte lipolysisT2D developmentPatientsT2DBioactive proteinsMetabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance
Sun J, Zhang Y, Zhang Q, Hu L, Zhao L, Wang H, Yuan Y, Niu H, Wang D, Zhang H, Liu J, Feng X, Su X, Qiu J, Sun J, Xu H, Zhang C, Wang K, Bi Y, Engleman E, Shen L. Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance. Immunity 2024, 57: 1289-1305.e9. PMID: 38772366, DOI: 10.1016/j.immuni.2024.04.024.Peer-Reviewed Original ResearchLiver kinase B1PD-1 expressionLKB1 deficiencyInsulin resistanceSuppressing Bcl-xL expressionBcl-xL expressionGroup 2 innate lymphoid cellsBlockade of PD-1Treatment of metabolic diseasesObesity-induced insulin resistanceFunction of ILC2sType 2 immunityMitochondrial homeostasisActivation of NFATObesity-associated insulin resistanceMitochondrial metabolismPrevent insulin resistanceKinase B1Exacerbate insulin resistanceEnhanced mitophagyMetabolic homeostasisILC2 responsesPD-1Genetic ablationLymphoid cellsTlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson J, Hu Y, Zhao H, Wong F, Wang Q, Wen L. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 2024, 15: 4232. PMID: 38762479, PMCID: PMC11102548, DOI: 10.1038/s41467-024-48611-8.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Gut microbiotaGut microbial communityTransferred to germ-free miceB cellsGerm-free miceTLR9 deficiencyKO miceGene sequencesGerminal center B cellsMicrobial communitiesMarginal zone B cellsGut dysbiosisFollicular helper cellsSelf-DNAMetabolic homeostasisAssociated with increased frequencyPro-inflammatory stateFat tissue inflammationGutHigh-fat dietMicrobiotaHelper cellsT cellsControl mice
2023
MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis.
Park J, Hall C, Hubbard B, LaMoia T, Gaspar R, Nasiri A, Li F, Zhang H, Kim J, Haeusler R, Accili D, Shulman G, Yu H, Choi E. MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis. Diabetes 2023, 72: 1781-1794. PMID: 37725942, PMCID: PMC10658066, DOI: 10.2337/db23-0314.Peer-Reviewed Original ResearchConceptsIR endocytosisInsulin receptor endocytosisCell division regulatorsInsulin receptorProlongs insulin actionReceptor endocytosisTranscriptomic profilesInsulin stimulationEndocytosisMetabolic homeostasisCell surfaceGenetic ablationMetabolic functionsInsulin actionP31cometMad2BubR1DisruptionSignalingRegulatorHomeostasisAdipose tissueInteractionHepatic fat accumulationMetabolism
2022
Bioactive lipids and metabolic syndrome—a symposium report
DeVito LM, Dennis EA, Kahn BB, Shulman GI, Witztum JL, Sadhu S, Nickels J, Spite M, Smyth S, Spiegel S. Bioactive lipids and metabolic syndrome—a symposium report. Annals Of The New York Academy Of Sciences 2022, 1511: 87-106. PMID: 35218041, PMCID: PMC9219555, DOI: 10.1111/nyas.14752.Peer-Reviewed Original ResearchConceptsBioactive lipidsMetabolic syndromeCardiometabolic conditionsCardiovascular diseaseAnimal modelsDietary lipidsLipid metabolismMetabolic homeostasisMultitude of functionsLipidomic approachLipid pathwaysContinued investigationSyndromeMolecular functionsSymposium reportGenetic studiesLipidsPathwayInflammationGreater understandingDiseaseLiverMacrophagesLipogenesis
2020
Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity
Brestoff JR, Wilen CB, Moley JR, Li Y, Zou W, Malvin NP, Rowen MN, Saunders BT, Ma H, Mack MR, Hykes BL, Balce DR, Orvedahl A, Williams JW, Rohatgi N, Wang X, McAllaster MR, Handley SA, Kim BS, Doench JG, Zinselmeyer BH, Diamond MS, Virgin HW, Gelman AE, Teitelbaum SL. Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity. Cell Metabolism 2020, 33: 270-282.e8. PMID: 33278339, PMCID: PMC7858234, DOI: 10.1016/j.cmet.2020.11.008.Peer-Reviewed Original ResearchConceptsIntercellular mitochondria transferMitochondria transferMitochondria uptakeMetabolic homeostasisGenome-wide CRISPRWhite adipose tissue homeostasisWAT macrophagesDistinct macrophage subpopulationsKnockout screensTissue homeostasisHeparan sulfateAdipose tissue homeostasisWhite adipose tissueGenes EXT1HomeostasisImmunometabolic crosstalkMitochondriaAdipocytesMyeloid cellsMacrophage subpopulationsCellsVivoRecent studiesMacrophagesCRISPRMulti-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health
Abulizi A, Cardone RL, Stark R, Lewandowski SL, Zhao X, Hillion J, Ma L, Sehgal R, Alves TC, Thomas C, Kung C, Wang B, Siebel S, Andrews ZB, Mason GF, Rinehart J, Merrins MJ, Kibbey RG. Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health. Cell Metabolism 2020, 32: 751-766.e11. PMID: 33147485, PMCID: PMC7679013, DOI: 10.1016/j.cmet.2020.10.006.Peer-Reviewed Original ResearchConceptsInsulin secretionInsulin sensitivityPK activatorWhole-body metabolic healthPK activationMetabolic homeostasisPeripheral insulin sensitivityHFD-fed ratsEndogenous glucose productionPreclinical rodent modelsHigher insulin contentPreclinical rationaleLiver fatMetabolic healthMarkers of differentiationIslet functionRodent modelsGlucose homeostasisInsulin contentPancreatic isletsGlucose productionGlucose turnoverMitochondrial PEPCKSecretionHomeostasisIntroduction to the Physiology, Immunology and Pathology of the Liver and Biliary Tree
Carbone M, Strazzabosco M. Introduction to the Physiology, Immunology and Pathology of the Liver and Biliary Tree. 2020, 3-20. DOI: 10.1002/9781119532637.ch1.Peer-Reviewed Original ResearchBile acidsBile formationDietary lipid absorptionMetabolism of bilirubinBiliary tree stem cellsBiliary treeLiver synthesisHepatic metabolismLipid absorptionEnergy homeostasisCholesterol homeostasisMetabolic homeostasisLiverCanalicular secretionStem cellsSecretionHomeostasisRegenerative abilityMetabolismBilirubinPathologyEndotoxinImmunology
2019
Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis
Camell CD, Günther P, Lee A, Goldberg EL, Spadaro O, Youm YH, Bartke A, Hubbard GB, Ikeno Y, Ruddle NH, Schultze J, Dixit VD. Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis. Cell Metabolism 2019, 30: 1024-1039.e6. PMID: 31735593, PMCID: PMC6944439, DOI: 10.1016/j.cmet.2019.10.006.Peer-Reviewed Original ResearchConceptsAge-associated B cellsFat-associated lymphoid clustersB cellsAdipose tissue leukocytesB-cell depletionB cell accumulationBody temperature maintenanceFALC formationVisceral adiposityCell depletionNLRP3 inflammasomeFemale miceLymphoid clustersMetabolic dysfunctionIL-1Metabolic impairmentIL-1RTissue leukocytesCell accumulationMetabolic homeostasisUnique populationLipolysisCellsTemperature maintenanceAdiposityGlutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis
Chen Y, Manna SK, Golla S, Krausz KW, Cai Y, Garcia-Milian R, Chakraborty T, Chakraborty J, Chatterjee R, Thompson DC, Gonzalez FJ, Vasiliou V. Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis. Free Radical Biology And Medicine 2019, 143: 127-139. PMID: 31351176, PMCID: PMC6848780, DOI: 10.1016/j.freeradbiomed.2019.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl Coenzyme AAlcohol DrinkingAMP-Activated Protein KinasesAnimalsEthanolFatty AcidsFatty LiverGlucuronic AcidGlutamate-Cysteine LigaseGlutamatesGlutathioneHomeostasisLipogenesisLiverMaleMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisOxidation-ReductionOxidative StressPentose Phosphate PathwayProtective AgentsTranscription, GeneticConceptsGlutamate-cysteine ligase modifier subunit geneProtein kinase pathwayAcetyl-CoA fluxMultiple cellular pathwaysAlcohol-induced steatosisCellular stressNucleotide biosynthesisLiver microarray analysisGlobal profilingSubunit geneCellular pathwaysMetabolic reprogrammingKinase pathwayMicroarray analysisMolecular mechanismsGSH poolCellular responsesMetabolic pathwaysLower GSHMolecular pathwaysMetabolic homeostasisAmino acidsDepletion of glutathioneCritical pathogenic eventGlucuronate pathwayAnti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance
Camporez JP, Lyu K, Goldberg EL, Zhang D, Cline GW, Jurczak MJ, Dixit VD, Petersen KF, Shulman GI. Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance. The Journal Of Physiology 2019, 597: 3885-3903. PMID: 31206703, PMCID: PMC6876753, DOI: 10.1113/jp277270.Peer-Reviewed Original ResearchConceptsObesity-induced insulin resistanceHigh-fat dietEctopic lipid contentWhite adipose tissue lipolysisInsulin resistanceAdipose tissue lipolysisMale miceInsulin sensitivityFemale miceInsulin-stimulated suppressionWAT inflammationTissue lipolysisRodent studiesTumor necrosis factor αWhole-body insulin sensitivityLipid-induced insulin resistanceMetabolic homeostasisAge-matched menInterleukin-6 concentrationsSkeletal muscleAnti-inflammatory effectsType 2 diabetesInsulin-mediated suppressionSexual dimorphic responseNecrosis factor αHepatic metabolic adaptation in a murine model of glutathione deficiency
Chen Y, Golla S, Garcia-Milian R, Thompson DC, Gonzalez FJ, Vasiliou V. Hepatic metabolic adaptation in a murine model of glutathione deficiency. Chemico-Biological Interactions 2019, 303: 1-6. PMID: 30794799, PMCID: PMC6743730, DOI: 10.1016/j.cbi.2019.02.015.Peer-Reviewed Original ResearchConceptsCellular non-protein thiolsMetabolic adaptationGlutamate-cysteine ligase modifier subunitNon-protein thiolsHepatic metabolic adaptationCellular redoxGlobal profilingGSH homeostasisModifier subunitLiver developmentBiochemical mechanismsMetabolic homeostasisAmino acidsGclm null miceDefense mechanismsEnvironmental insultsOxidative damageFatty liver developmentNull miceSpectrum of changesNucleic acidsMetabolic signaturesPivotal roleHomeostasisGlutathione deficiency
2018
A review of brain insulin signaling in mood disorders: From biomarker to clinical target
Nguyen T, Chan L, Borreginne K, Kale R, Hu C, Tye S. A review of brain insulin signaling in mood disorders: From biomarker to clinical target. Neuroscience & Biobehavioral Reviews 2018, 92: 7-15. PMID: 29758232, DOI: 10.1016/j.neubiorev.2018.05.014.Peer-Reviewed Original ResearchConceptsMood disordersCentral insulin signalingInsulin signalingSevere mood disordersBrain insulin signalingSynaptic plasticity processesPoor treatment outcomesInsulin signaling pathwayMood regulationMetabolic dysfunctionNeurotrophic processesMoodSevere disease courseBidirectional relationshipCellular metabolismInsulin receptor expressionMetabolic homeostasisSignaling pathwayMetabolic processesPrecision medicine approachMechanistic overlapTreatment outcomesMetabolic functionsDisordersBiomarker-based diagnostics
2017
Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat
Damgaard M, Pærregaard S, Søgaard I, Agerholm M, Paulson J, Treebak J, Sina C, Holm J, Kristiansen K, Jensen B. Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat. The Journal Of Nutritional Biochemistry 2017, 54: 66-76. PMID: 29268121, DOI: 10.1016/j.jnutbio.2017.09.026.Peer-Reviewed Original ResearchConceptsGlucose homeostasisGut microbial alterationsGene amplicon sequencingInfluence of dietary fat sourceLow-fat dietAmplicon sequencingFatty acidsGut microbiotaResponse to insulinDietary fat sourceMicrobial alterationsAssessed glucose homeostasisMetabolic homeostasisDietary fatGlucose clearanceGlucose regulationLFD-fed miceFat sourcesHomeostasisFish oilGroups of miceInsulin tolerance testWeek 8 to weekSoybean oilSevere nonalcoholic steatohepatitisPuberty is an important developmental period for the establishment of adipose tissue mass and metabolic homeostasis
Holtrup B, Church CD, Berry R, Colman L, Jeffery E, Bober J, Rodeheffer MS. Puberty is an important developmental period for the establishment of adipose tissue mass and metabolic homeostasis. Adipocyte 2017, 6: 224-233. PMID: 28792785, PMCID: PMC5638358, DOI: 10.1080/21623945.2017.1349042.Peer-Reviewed Original ResearchConceptsChildhood obesityMetabolic dysfunctionMetabolic homeostasisObesogenic stimuliExposure of miceHigh-fat dietAdipose tissue functionAdipose tissue massPostnatal day 18White adipose tissueType II diabetesCritical developmental periodAdipose massFat dietLeptin expressionAdipocyte sizeFat massDiabetic phenotypeObesityTissue massAdipose tissueBody weightDay 18II diabetesAdipose functionCarnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation
Goldberg EL, Dixit VD. Carnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation. Molecular Metabolism 2017, 6: 219-225. PMID: 28180063, PMCID: PMC5279934, DOI: 10.1016/j.molmet.2016.12.008.Peer-Reviewed Original ResearchConceptsNutrient stressFatty acid oxidationAcyl-CoA poolMacrophage energy metabolismAcid oxidationMetabolic stressorsMyeloid lineage cellsStress sensingSwitch mechanismMetabolic homeostasisLineage cellsEnergy metabolismImportant unanswered questionsMuscle cellsHomeostasisCRATHigh-fat diet-induced obesityAcetyltransferase expressionDiet-induced obesityGlucose homeostasisTissue leukocytosisMacrophagesCellsLittermate controlsUnanswered questions
2016
The role of astrocytes in the hypothalamic response and adaptation to metabolic signals
Chowen JA, Argente-Arizón P, Freire-Regatillo A, Frago LM, Horvath TL, Argente J. The role of astrocytes in the hypothalamic response and adaptation to metabolic signals. Progress In Neurobiology 2016, 144: 68-87. PMID: 27000556, DOI: 10.1016/j.pneurobio.2016.03.001.Peer-Reviewed Original ResearchConceptsHypothalamic responseMetabolic signalsRole of astrocytesIncidence of obesityAnorexigenic hormone leptinType 2 diabetesHypothalamic adaptationsImportant metabolic signalsDiabetes mellitusHypothalamic circuitsSecondary complicationsChronic conditionsHormone leptinGlial cellsSynaptic transmissionAdequate treatmentMetabolic diseasesSynaptic plasticityNeuroendocrine controlHomeostatic functionsNeighboring neuronsMetabolic homeostasisHormonal inputsObesityHypothalamus
2014
Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling
Waterson MJ, Chung BY, Harvanek ZM, Ostojic I, Alcedo J, Pletcher SD. Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 8137-8142. PMID: 24821805, PMCID: PMC4050545, DOI: 10.1073/pnas.1315461111.Peer-Reviewed Original ResearchConceptsMetabolic homeostasisAdipokinetic hormone signalingDrosophila lifespanHormone signalingAKH receptorMutant effectsMetabolic shiftPhysiological homeostasisHealthy lifespanMetabolic waterWater availabilityHomeostasisAKHGustatory systemLifespanGustatory signalsInternal lipidsCentral nervous system integrationEndocrine systemTaxaSensory regulationLong-term healthWater storesSignalingPhysiologyPigment Epithelium-Derived Factor (PEDF) Suppresses IL-1β-Mediated c-Jun N-Terminal Kinase (JNK) Activation to Improve Hepatocyte Insulin Signaling
Gattu AK, Birkenfeld AL, Iwakiri Y, Jay S, Saltzman M, Doll J, Protiva P, Samuel VT, Crawford SE, Chung C. Pigment Epithelium-Derived Factor (PEDF) Suppresses IL-1β-Mediated c-Jun N-Terminal Kinase (JNK) Activation to Improve Hepatocyte Insulin Signaling. Endocrinology 2014, 155: 1373-1385. PMID: 24456163, PMCID: PMC5393334, DOI: 10.1210/en.2013-1785.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsEye ProteinsGene Expression RegulationGlucose Tolerance TestHepatocytesHumansInflammationInsulinInsulin ResistanceInterleukin-1betaJNK Mitogen-Activated Protein KinasesLiverMaleMetabolic SyndromeMetabolomicsMiceMice, Inbred C57BLMice, KnockoutMicrospheresNerve Growth FactorsObesityPalmitic AcidPhenotypeRNA InterferenceSerpinsSignal TransductionSuccinic AcidConceptsPigment epithelium-derived factorKO miceMetabolic syndromeIL-1βC-Jun N-terminal kinase (JNK) activationElevated pigment epithelium-derived factorIL-1β challengeHuman hepatocytesIL-1β expressionHuman metabolic syndromeEpithelium-derived factorPEDF-knockout miceInflammatory markersGlucose intoleranceSerum levelsC-Jun N-terminal kinaseKinase activationAntiinflammatory proteinHepatic insulinKnockout micePigment epitheliumN-terminal kinaseMiceSyndromeMetabolic homeostasis
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