2025
B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity
Puente-Ruiz S, Ide L, Schuller J, Ben-Kraiem A, Hoffmann A, Ghosh A, Noé F, Wolfrum C, Krause K, Gericke M, Klöting N, Brüning J, Wunderlich F, Blüher M, Jais A. B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity. IScience 2025, 28: 112819. DOI: 10.1016/j.isci.2025.112819.Peer-Reviewed Original ResearchMacrophage recruitmentMetabolic inflammationGlucose toleranceEffects of nociceptin/orphanin FQInsulin resistanceN/OFQ-NOP systemAdverse metabolic effectsImpaired glucose toleranceImmune cell migrationDiet-induced obesityNociceptin/orphanin FQB cellsEnhanced insulin sensitivityKnockout miceOpioid peptidesImmune regulationGlucose intoleranceMetabolic effectsImmunomodulatory propertiesInflammatory processN/OFQInsulin sensitivityObesityTherapeutic targetAdipose tissue214-OR: Increases in TUG Abundance and Expression Are a Feature of Insulin-Resistant Human Adipose Tissue
STROBER J, TER HORST K, SLUSHER A, PAULO J, GASSAWAY B, SHUKEN S, CAPRIO S, SERLIE M, BOGAN J, VATNER D. 214-OR: Increases in TUG Abundance and Expression Are a Feature of Insulin-Resistant Human Adipose Tissue. Diabetes 2025, 74 DOI: 10.2337/db25-214-or.Peer-Reviewed Original ResearchWhite adipose tissueHuman white adipose tissueInsulin signalingInsulin resistanceInsulin-stimulated Akt phosphorylationInsulin-responsive GLUT4Pathogenesis of metabolic diseasesTUG cleavageFructose-sweetened beveragesBariatric surgery cohortMetabolic diseasesCohort of patientsAdipose tissueProteomic analysisHuman IRGene expressionMolecular regulationPathway proteinsHyperinsulinemic euglycemic clampAkt phosphorylationSurgery cohortBariatric surgeryHuman adipose tissueNational Institutes of HealthTC10FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression
Gliniak C, Gordillo R, Youm Y, Lin Q, Crewe C, Zhang Z, Field B, Fujikawa T, Virostek M, Zhao S, Zhu Y, Rosen C, Horvath T, Dixit V, Scherer P. FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression. Cell Metabolism 2025, 37: 1547-1567.e6. PMID: 40527315, DOI: 10.1016/j.cmet.2025.05.011.Peer-Reviewed Original ResearchInflammatory immune cellsVisceral adipose tissueDiet-induced obesityAged transgenic miceHigh-fat dietAbsence of adiponectinTreat metabolic syndromeFibroblast growth factor 21Immune cellsLipotoxic ceramidesMetabolic syndromeReduced liver steatosisTransgenic miceMetabolic profileMetabolic benefitsInsulin sensitivityLiver steatosisIn adulthoodAdipose tissueMiceFat tissueImprove metabolismGrowth suppressionMetabolic issuesAge-related diseasesCysteine depletion triggers adipose tissue thermogenesis and weight loss
Lee A, Orliaguet L, Youm Y, Maeda R, Dlugos T, Lei Y, Coman D, Shchukina I, Andhey P, Smith S, Ravussin E, Stadler K, Chen B, Artyomov M, Hyder F, Horvath T, Schneeberger M, Sugiura Y, Dixit V. Cysteine depletion triggers adipose tissue thermogenesis and weight loss. Nature Metabolism 2025, 7: 1204-1222. PMID: 40461845, PMCID: PMC12198010, DOI: 10.1038/s42255-025-01297-8.Peer-Reviewed Original ResearchConceptsWeight lossWhite adipose tissueAdipose browningCaloric restrictionAdipose tissueDietary amino acidsCysteine depletionSulphur amino acids cysteineIncreased energy expenditureAdipose tissue thermogenesisIncreased fat utilizationMetabolic inflammationNoradrenaline signalingOrganismal metabolismAdipose thermogenesisObese miceBrowning of adipocytesIncreased heat productionBrownRemoval of cysteineCore body temperatureAmino acidsEnergy expenditureAmino acid cysteineFat utilizationThe subfornical organ is a nucleus for gut-derived T cells that regulate behaviour
Yoshida T, Nguyen M, Zhang L, Lu B, Zhu B, Murray K, Mineur Y, Zhang C, Xu D, Lin E, Luchsinger J, Bhatta S, Waizman D, Coden M, Ma Y, Israni-Winger K, Russo A, Wang H, Song W, Al Souz J, Zhao H, Craft J, Picciotto M, Grutzendler J, Distasio M, Palm N, Hafler D, Wang A. The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour. Nature 2025, 1-10. PMID: 40437096, DOI: 10.1038/s41586-025-09050-7.Peer-Reviewed Original ResearchMeningeal T cellsCentral nervous systemT cellsSubfornical organCD4 T cellsInnate immune compartmentGut-brain axisSteady-state brainGut microbiotaSpecialized immune cellsCentral nervous system homeostasisAdaptive immune systemBiological functionsImmune compartmentGut-derived T cellsImmune cellsWhite adiposeImmune systemNervous systemAdipose tissueComposition of adipose tissueGastrointestinal tissuesWell-characterizedHomeostasisBrainCharacterization and lineage tracing of a mouse adipose depot reveal properties conserved with human supraclavicular brown adipose tissue
Li L, Feldman B. Characterization and lineage tracing of a mouse adipose depot reveal properties conserved with human supraclavicular brown adipose tissue. Stem Cell Reports 2025, 20: 102509. PMID: 40409261, PMCID: PMC12181967, DOI: 10.1016/j.stemcr.2025.102509.Peer-Reviewed Original ResearchConceptsInguinal white adipose tissueBrown adipose tissueSupraclavicular brown adipose tissuePreclinical modelsAdipose tissueActivation of beige adipocytesBeige adipose tissueAdipose tissue developmentWhite adipose tissueRobust preclinical modelsBeige fatDevelopmental originsMolecular markersSuccess of therapyTissue developmentThermogenic activityAdipose tissue depotsLineage tracingCell originLineagesAdipose depotsTherapeutic benefitMetabolic disordersTissue depotsMiceImmunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease
Shen H, Liangpunsakul S, Iwakiri Y, Szabo G, Wang H. Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease. Cellular & Molecular Immunology 2025, 1-15. PMID: 40399593, DOI: 10.1038/s41423-025-01291-w.Peer-Reviewed Original ResearchAlcohol-associated liver diseaseTherapeutic targetLiver diseaseOptimal treatment strategyAnti-inflammatory therapyNon-parenchymal liver cellsExtra-hepatic organsImprove patient outcomesImmune cellsImmunological mechanismsInflammatory cellsImmunological pathwaysTreatment strategiesInflammatory mediatorsDisease onsetGlobal health challengePatient outcomesNervous systemInflammationAdipose tissueLiver cellsPrecision medicineClinical researchDiseaseHealth challengesAI-based volumetric six-tissue body composition quantification from CT cardiac attenuation scans for mortality prediction: a multicentre study
Yi J, Marcinkiewicz A, Shanbhag A, Miller R, Geers J, Zhang W, Killekar A, Manral N, Lemley M, Buchwald M, Kwiecinski J, Zhou J, Kavanagh P, Liang J, Builoff V, Ruddy T, Einstein A, Feher A, Miller E, Sinusas A, Berman D, Dey D, Slomka P. AI-based volumetric six-tissue body composition quantification from CT cardiac attenuation scans for mortality prediction: a multicentre study. The Lancet Digital Health 2025, 7: 100862. PMID: 40382274, PMCID: PMC12126277, DOI: 10.1016/j.landig.2025.02.002.Peer-Reviewed Original ResearchConceptsCT attenuation correctionEpicardial adipose tissueVisceral adipose tissuePrognostic valueAdipose tissuePerfusion imagingMedian follow-up timeHigher visceral adipose tissueIncreased all-cause mortality riskMuscle volume indexAttenuation correctionPredicting all-cause mortalityCardiac perfusion imagingKaplan-Meier curvesAll-cause mortality riskBody composition measurementsCox regression modelsAll-cause mortalityReduced riskVolumetric measurementsIntramuscular adipose tissueMortality risk stratificationAI-based segmentationSubcutaneous adipose tissueIndex volumeTowards a consensus atlas of human and mouse adipose tissue at single-cell resolution
Loft A, Emont M, Weinstock A, Divoux A, Ghosh A, Wagner A, Hertzel A, Maniyadath B, Deplancke B, Liu B, Scheele C, Lumeng C, Ding C, Ma C, Wolfrum C, Strieder-Barboza C, Li C, Truong D, Bernlohr D, Stener-Victorin E, Kershaw E, Yeger-Lotem E, Shamsi F, Hui H, Camara H, Zhong J, Kalucka J, Ludwig J, Semon J, Jalkanen J, Whytock K, Dumont K, Sparks L, Muir L, Fang L, Massier L, Saraiva L, Beyer M, Jeschke M, Mori M, Boroni M, Walsh M, Patti M, Lynes M, Blüher M, Rydén M, Hamda N, Solimini N, Mejhert N, Gao P, Gupta R, Murphy R, Pirouzpanah S, Corvera S, Tang S, Das S, Schmidt S, Zhang T, Nelson T, O’Sullivan T, Efthymiou V, Wang W, Tong Y, Tseng Y, Mandrup S, Rosen E. Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution. Nature Metabolism 2025, 7: 875-894. PMID: 40360756, DOI: 10.1038/s42255-025-01296-9.Peer-Reviewed Original ResearchConceptsCell annotationSingle-cell dataRegulation of metabolic homeostasisSingle-cell resolutionSingle-cell atlasMouse adipose tissueAdipose tissueMetabolic homeostasisSpecialized cellsPrimary repositoryAnnotationCellsExcess caloriesBionetworkProportion of adipocytesConnective tissueMiceTissueComplex connective tissueAdipocytesHomeostasisMyeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity
Hof A, Landerer M, Peitsmeyer P, Herzog R, Alber J, Ahdab M, Nettersheim F, Mehrkens D, Geißen S, Braumann S, Guthoff H, von Stein P, Nemade H, Picard F, Braun R, Hoyer F, Brüning J, Pfeifer A, Hildebrand S, Winkels H, Baldus S, Adam M, Schäkel J, Mollenhauer M. Myeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity. Cell Reports Medicine 2025, 6: 102087. PMID: 40252642, PMCID: PMC12147848, DOI: 10.1016/j.xcrm.2025.102087.Peer-Reviewed Original ResearchConceptsPerivascular adipose tissueVascular functionEndothelial functionObesity-related cardiovascular diseaseImmune cell frequenciesAdipose tissuePerivascular adipose tissue inflammationReduced arterial stiffnessInflammatory cytokine releaseHuman white adipocytesInfluence vascular functionObese patientsAdipocyte marker expressionMyeloid cellsCardiovascular morbidityImmune cellsCytokine releaseEndothelial dysfunctionIncreased inflammationAdipocyte secretomeCell frequencyMarker expressionMPO levelsConsumption in vivoNitrotyrosine formationATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis
Slusher A, Santoro N, Vash-Margita A, Galderisi A, Hu P, Tokoglu F, Li Z, Tarabra E, Strober J, Vatner D, Shulman G, Caprio S. ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis. Journal Of Clinical Investigation 2025, 135: e184740. PMID: 40091831, PMCID: PMC11910223, DOI: 10.1172/jci184740.Peer-Reviewed Original ResearchConceptsHyperinsulinemic-euglycemic clampSubcutaneous adipose tissueInsulin resistanceAdipose triglyceride lipaseInsulin infusionOral glucose tolerance testAbdominal fat distributionGlucose tolerance testMeasuring abdominal fat distributionLower liver fatActivating adipose triglyceride lipaseMetabolic disease riskLiver fat contentEctopic lipid storageFUNDINGThis workAdipose tissue lipolysisInhibition of adipose tissue lipolysisSubcutaneous adipose tissue samplesFat distributionTolerance testInsulin exposureLiver fatInfusionGlycerol turnoverAdipose tissueThe metabolic and cardiovascular effects of amphetamine are partially mediated by the central melanocortin system
Simonds S, Pryor J, Lam B, Dowsett G, Mustafa T, Munder A, Elysee K, Balland E, Cowley L, Yeo G, Lawrence A, Spanswick D, Cowley M. The metabolic and cardiovascular effects of amphetamine are partially mediated by the central melanocortin system. Cell Reports Medicine 2025, 6: 101936. PMID: 39914386, PMCID: PMC11866487, DOI: 10.1016/j.xcrm.2025.101936.Peer-Reviewed Original ResearchConceptsEffects of amphetamineCentral melanocortin systemCardiovascular effectsMelanocortin systemFood intakeInhibition of POMC neuronsAMPH-induced anorexiaMelanocortin 4 receptor-deficientNoradrenergic neurotransmitter systemsHeart rateBrown adipose tissueElevated blood pressureBody weightNoradrenergic inhibitionPOMC neuronsAMPH-inducedSerotonergic activityPresynaptic mechanismsNeurotransmitter systemsMC4R pathwayAmphetamineBlood pressureCardiovascular functionIncreased brown adipose tissueAdipose tissueFGF21 regulates ceramide levels preferentially in visceral vs. subcutaneous white adipose tissue in aged mice fed a high-fat diet
Gliniak C, Gordillo R, Field B, Dixit V, Scherer P. FGF21 regulates ceramide levels preferentially in visceral vs. subcutaneous white adipose tissue in aged mice fed a high-fat diet. Physiology 2025, 40: 1588. DOI: 10.1152/physiol.2025.40.s1.1588.Peer-Reviewed Original Research
2024
Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity
Galuppo B, Mannam P, Bonet J, Pierpont B, Trico’ D, Haskell-Luevano C, Ericson M, Freeman K, Philbrick W, Bale A, Caprio S, Santoro N. Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity. International Journal Of Obesity 2024, 49: 819-826. PMID: 39738493, PMCID: PMC12095050, DOI: 10.1038/s41366-024-01706-0.Peer-Reviewed Original ResearchOral glucose tolerance testVisceral adipose tissueMelanocortin-4 receptor geneSubcutaneous adipose tissueVariant groupYale Pediatric Obesity ClinicInsulin resistanceEarly-onset obesityBMI z-scorePediatric obesity clinicRare variantsAdipose tissueAbdominal fat distributionDegree of obesityGlucose tolerance testTotal body fatIntrahepatic fat contentLower insulin sensitivityIntrahepatic fat accumulationAssociated with abdominal fatAbdominal MRIObesity clinicMetabolic sequelaePathogenic variantsFat distributionInsulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial
Nadeau K, Arslanian S, Bacha F, Caprio S, Chao L, Farrell R, Hughan K, Rayas M, Tung M, Cross K, El ghormli L. Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial. Diabetologia 2024, 68: 676-687. PMID: 39706874, DOI: 10.1007/s00125-024-06327-w.Peer-Reviewed Original ResearchConceptsYouth-onset type 2 diabetesType 2 diabetesBeta cell functionRandomised clinical trialsVisceral adipose tissueMarkers of adiposityInsulin sensitivityInsulin clearanceSubcutaneous adipose tissueCell functionClinical trialsResponse to rosiglitazone treatmentDual-energy X-ray absorptiometryPersistently elevated blood glucose levelsMarkers of insulin sensitivityFasting blood testsX-ray absorptiometryFasting C-peptideNon-Hispanic black raceAdipose tissueResponse to treatmentCompensatory response to changesElevated blood glucose levelsNational Institute of DiabetesSecondary analysisMyoid Hamartoma of the Breast With HMGA2 Rearrangement and Associated In-Situ and Invasive Carcinoma: Case Report and Review of Literature
Ines F, Marketkar S, Ng S, Manrai P, Sung C, Bridge J, Singh K. Myoid Hamartoma of the Breast With HMGA2 Rearrangement and Associated In-Situ and Invasive Carcinoma: Case Report and Review of Literature. International Journal Of Surgical Pathology 2024, 33: 689-699. PMID: 39471995, DOI: 10.1177/10668969241271420.Peer-Reviewed Original ResearchMyoid hamartomaInvasive carcinomaGene rearrangementsLikelihood of malignant transformationBenign breast neoplasmsBenign clinical courseFluorescence in situ hybridization analysisRare breast lesionSmooth muscle bundlesClinical courseStromal compartmentCase reportOverexpression of HMGA2Breast lesionsMalignant transformationRadiological studiesBreast neoplasmsHMGA2 rearrangementsAncillary testsProtein overexpressionHamartomaMolecular findingsStromal cellsAnechoic areasAdipose tissueSustained caloric restriction potentiates insulin action by activating prostacyclin synthase
Merali C, Quinn C, Huffman K, Pieper C, Bogan J, Barrero C, Merali S. Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase. Obesity 2024, 32: 2286-2298. PMID: 39420421, PMCID: PMC12034231, DOI: 10.1002/oby.24150.Peer-Reviewed Original ResearchMolecular mechanismsIncreased GLUT4 translocationComplex molecular mechanismsGlucose uptake regulationUBX domainIncreased glucose uptakeGLUT4 translocationGLUT4 functionCaloric restrictionPTGIS expressionProteomic profilingCell surfaceCleavage pathwayInsulin sensitivityHuman adipocytesAdipose tissueGlucose uptakeGLUT4Enhanced insulin sensitivityInsulin receptor densityInsulin actionRisk of metabolic disordersCell membraneProstacyclin synthaseMonths of CRDownregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissueThe subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose
Mashayekhi M, Sheng Q, Bailin S, Massier L, Zhong J, Shi M, Wanjalla C, Wang T, Ikizler T, Niswender K, Gabriel C, Palacios J, Turgeon‐Jones R, Reynolds C, Luther J, Brown N, Das S, Dahlman I, Mosley J, Koethe J, Rydén M, Bachmann K, Shah R. The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose. Obesity 2024, 32: 1526-1540. PMID: 38967296, PMCID: PMC11269023, DOI: 10.1002/oby.24064.Peer-Reviewed Original ResearchVisceral adipose tissueExpression quantitative trait lociSubcutaneous adipose tissueGenetic effect sizesQuantitative trait lociInsulin resistanceAdipocyte transcriptsSat geneAdipose transcriptomeTrait lociTranscriptional architectureTranscriptional landscapeMetabolic bufferRNA sequencingInsulin stimulationAdipose tissueNon-immune cell populationsMetabolic phenotypeWeight loss surgeryNon-immune populationSpectrum of obesityCardiometabolic disease riskMacrophage transcriptionMolecular signaturesType 2 diabetesComputational modeling of the physical features that influence breast cancer invasion into adipose tissue
Zheng Y, Wang D, Beeghly G, Fischbach C, Shattuck M, O'Hern C. Computational modeling of the physical features that influence breast cancer invasion into adipose tissue. APL Bioengineering 2024, 8: 036104. PMID: 38966325, PMCID: PMC11223776, DOI: 10.1063/5.0209019.Peer-Reviewed Original ResearchBreast cancer invasionCancer cellsMechanical propertiesCancer invasionDiscrete element method simulationsMechanical properties of cancer cellsProperties of cancer cellsElement method simulationsCancer cell invasionAdipose tissueDegree of invasionCohesive spherical particlesBiochemical signalsMethod simulationsCell invasionMaster curveSpherical particlesExtracellular matrixAdipocytesInfluence disease progressionSystem pressureDeformable polyhedronInvasionDe-mixingCells
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