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 tissueUptake of and Disparities in Semaglutide and Tirzepatide Prescribing for Obesity in the US
Kim C, Ross J, Jastreboff A, Meeker D, Freedman H, Krumholz H, Lu Y. Uptake of and Disparities in Semaglutide and Tirzepatide Prescribing for Obesity in the US. JAMA 2025, 333: 2203-2206. PMID: 40299371, PMCID: PMC12042086, DOI: 10.1001/jama.2025.4735.Peer-Reviewed Original ResearchOnce-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial
Jastreboff A, Ryan D, Bays H, Ebeling P, Mackowski M, Philipose N, Ross L, Liu Y, Burns C, Abbasi S, Pannacciulli N. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. New England Journal Of Medicine 2025 PMID: 40549887, DOI: 10.1056/nejmoa2504214.Peer-Reviewed Original ResearchBaseline to weekDose escalationTreatment of obesityTreatment policy estimandType 2 diabetesObese cohortBody weightDose-ranging trialPhase 2 trialGastrointestinal adverse eventsGlycated hemoglobin levelsPeptide-antibody conjugatesGlucagon-like peptide-1 receptor agonismIntention-to-treat approachOnce-monthlyDouble-blindPlacebo groupPlacebo-controlledReceptor antagonismReceptor agonismHemoglobin levelsAdverse eventsPlaceboSafety signalsObesityTirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT‐MMO trial
Lam C, Rodriguez A, Aminian A, Ferrannini E, Heerspink H, Jastreboff A, Laffin L, Pandey A, Ray K, Ridker P, Sanyal A, Yki‐Jarvinen H, Mason D, Strzelecki M, Bartee A, Cui C, Hurt K, Linetzky B, Bunck M, Nissen S. Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT‐MMO trial. Obesity 2025 PMID: 40545827, DOI: 10.1002/oby.24332.Peer-Reviewed Original ResearchSecondary cardiovascular disease preventionCardiovascular disease preventionCardiovascular diseaseGlucagon-like peptide-1 receptor agonistsGlucose-dependent insulinotropic polypeptide receptorPeptide-1 receptor agonistsMultiple cardiovascular risk factorsCardiovascular risk factorsHeart failure eventsNonfatal myocardial infarctionType 2 diabetesReduction of morbidityDisease preventionDouble-blindPrimary endpointReceptor agonistsClinical benefitImprove morbidityObesityCoronary revascularizationRisk factorsOutcome trialsTirzepatideMultiple outcomesSubstantial weight reduction1170-P: Gender Identity, Racial/Ethnic Identity, and Health Behaviors—Which High Schoolers Are at Highest Risk for Type 2 Diabetes?
SHARER A, BRIMACOMBE M, OYOLA-CARTAGENA K, DOYLE R, FINCK C, OLEZESKI C, SANTOS M. 1170-P: Gender Identity, Racial/Ethnic Identity, and Health Behaviors—Which High Schoolers Are at Highest Risk for Type 2 Diabetes? Diabetes 2025, 74 DOI: 10.2337/db25-1170-p.Peer-Reviewed Original ResearchHealth behaviorsYouth Risk Behavior SurveyType 2 diabetesRisk of obesityRegression modelsBinary logistic regression modelTransgender youthLogistic regression modelsPhysical activityRacial/ethnic groupsDevelopment of type 2 diabetesRisk Behavior SurveyUnique stressorsHealthBehavior SurveyObesityMinority stress theoryHigh riskMinority stressNon-significant relationshipT2DYouthTreatment outcomesRiskGender identity1727-P: Reduced Aromatic Amino Acid Suppression during Acute Hyperglycemia in Young Adults with Obesity
MATSON B, GUNAWAN F, ROTHMAN D, MASON G, NEWGARD C, HWANG J. 1727-P: Reduced Aromatic Amino Acid Suppression during Acute Hyperglycemia in Young Adults with Obesity. Diabetes 2025, 74 DOI: 10.2337/db25-1727-p.Peer-Reviewed Original ResearchCentral nervous systemAcute hyperglycemiaLean controlsBrain glucose levelsMass spectrometry-based metabolomic profilingMeasured plasma amino acidsInsulin resistanceGlucose levelsBranched chain amino acidsPlasma amino acidsDevelopment of insulin resistanceAromatic amino acid levelsChain amino acidsAcid suppressionResponse to hyperglycemiaMetabolomic profilesImpaired suppressionHyperglycemic clampObesityInsulin sensitivityHyperglycemiaNervous systemAmino acid changesBrain glucoseHealthy adults1686-P: Novel Combination of a Mitochondrial Protonophore (MP) and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice
SRODA N, SHARMA M, MURAKAMI E, LOGAN C, WENG S, KIRBY B, MYERS R, SUBRAMANIAN M, SHULMAN G, VIJAYAKUMAR A. 1686-P: Novel Combination of a Mitochondrial Protonophore (MP) and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice. Diabetes 2025, 74 DOI: 10.2337/db25-1686-p.Peer-Reviewed Original ResearchLean massMitochondrial protonophoreDIO miceFood intakeFat mass lossReduced lean massWeight lossBody weightAcetyl-CoA carboxylase 2Obesity-associated disordersMale DIO miceFat massSemaglutideDiet-inducedNovel combinationObese miceMetabolic disordersEnhanced fatty acid oxidationMiceFatty acid oxidationEvaluation of combinationsObesityInhibitorsTreated withIntakeToll-like receptors in B cells and obesity
Wang P, Hou C, Wong F, Wen L. Toll-like receptors in B cells and obesity. Trends In Molecular Medicine 2025 PMID: 40527636, DOI: 10.1016/j.molmed.2025.05.005.Peer-Reviewed Original ResearchToll-like receptorsPathogen-associated molecular patternsB cellsDendritic cellsFunction of Toll-like receptorsActivation of dendritic cellsActivation of TLR signalingExcessive adipose tissue accumulationSignaling mechanisms of Toll-like receptorsT cell differentiationAdipose tissue accumulationContext of obesityMechanisms of Toll-like receptorsChronic inflammationInflammatory activityAdaptive immunityImmune responseMetabolic dysregulationTLR signalingImmune functionObesityTissue accumulationMetabolic diseasesMolecular patternsSignaling mechanismsIs there harm in behavioral lifestyle weight management for binge-eating disorder in patients with obesity: Findings from a randomized controlled trial
Grilo C, Ivezaj V, Yurkow S, Lydecker J. Is there harm in behavioral lifestyle weight management for binge-eating disorder in patients with obesity: Findings from a randomized controlled trial. Journal Of Psychosomatic Research 2025, 195: 112169. PMID: 40516275, DOI: 10.1016/j.jpsychores.2025.112169.Peer-Reviewed Original ResearchEating-disorder psychopathologyBinge-eating disorderIncreased symptomsSymptoms of binge eatingRandomized controlled trialsBinge-eating frequencyBinge eatingPsychopathologyRandomized to placeboBinge-eatingWeight managementPlaceboHeterogeneity of outcomesDisordersParticipantsPosttreatmentSecondary analysisFrequency of casesSymptomsClinical contextIndividual levelObesityControlled trialsSmall magnitudePatientsBiosocial Variation in Treatment Response to GLP-1s: Implications for Clinical Care and Health Policy
Horwitz R, Otaka S, Conroy A, Cullen M, Matory A, Singer B, Sim I. Biosocial Variation in Treatment Response to GLP-1s: Implications for Clinical Care and Health Policy. The American Journal Of Medicine 2025 PMID: 40393609, DOI: 10.1016/j.amjmed.2025.05.016.Peer-Reviewed Original ResearchTreatment-resistant obesityTrajectory of obesityResponse to treatmentObesity-related disordersRandomized controlled trialsReal-world evidence studiesTreatment responseClinical managementEvidence studiesGLP-1sControlled trialsPatientsObesityWeight lossBody weightPathogenesisAverage treatment responseHealth policyTreatmentPhysiological systemsLifestyle behavioral weight‐loss treatment for binge‐eating disorder in patients with obesity: where's the harm?
Yurkow S, Ivezaj V, Grilo C. Lifestyle behavioral weight‐loss treatment for binge‐eating disorder in patients with obesity: where's the harm? Obesity 2025, 33: 1058-1066. PMID: 40342236, PMCID: PMC12119222, DOI: 10.1002/oby.24289.Peer-Reviewed Original ResearchConceptsBinge-eating disorderED psychopathologyWeight loss treatmentExacerbate eating disordersBinge-eating frequencyPsychopathology scoresBinge eatingSymptoms of binge eatingBehavioral weight loss treatmentIncreased symptomsEating disordersPsychopathologyFollow-upDisordersPosttreatmentHeterogeneity of outcomesEatingSecondary analysisFrequency of casesCoexisting obesityClinical contextParticipantsIndividual levelBingeObesityHypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis
Solheim M, Stroganov S, Chen W, Subagia P, Bauder C, Wnuk-Lipinski D, Del Río-Martín A, Sotelo-Hitschfeld T, Beddows C, Klemm P, Dodd G, Lundh S, Secher A, Wunderlich F, Steuernagel L, Brüning J. Hypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis. Cell 2025, 188: 3550-3566.e22. PMID: 40273910, DOI: 10.1016/j.cell.2025.04.001.Peer-Reviewed Original ResearchConceptsLeptin's anorectic effectsDiet-induced hyperphagiaNeuropeptide Y (NPYAgouti-related peptideChemogenetic activationAnorectic effectLeptin regulates appetiteBody weightArcuate nucleusLEPR expressionHyperphagiaLeptin actionSuppress appetiteObese backgroundLeptinObesity therapeuticsObesityNeuronsEnergy homeostasisWeight gainNPYNeurocircuitryAppetiteExpressionPNoCsDietary oleic acid drives obesogenic adipogenesis via modulation of LXRα signaling
Wing A, Jeffery E, Church C, Goodell J, Saavedra-Peña R, Saha M, Holtrup B, Voisin M, Alavi N, Floody M, Wang Z, Zapadka T, Garabedian M, Varshney R, Rudolph M, Rodeheffer M. Dietary oleic acid drives obesogenic adipogenesis via modulation of LXRα signaling. Cell Reports 2025, 44: 115527. PMID: 40208790, PMCID: PMC12073628, DOI: 10.1016/j.celrep.2025.115527.Peer-Reviewed Original ResearchAdipocyte precursor cellsDietary fatPlasma monounsaturated fatty acidsAssociated with human obesityHuman adipocyte precursor cellsMonounsaturated fatty acidsDietary fat compositionDietary screeningFatty acidsDietary fatty acidsHuman obesityAdipose expansionMetabolic healthObesity epidemicAkt2 signalingLXR activationPrecursor cellsAdipose biologyOleic acidHyperplasiaObesityAdipocyte hyperplasiaDietary oleic acidPhysiological regulationAdipogenesisDoes BMI matter when treating depression with esketamine? A retrospective analysis of real-world data
Ansari M, Rhee T, Santucci M, Nikayin S. Does BMI matter when treating depression with esketamine? A retrospective analysis of real-world data. Journal Of Affective Disorders 2025, 381: 22-28. PMID: 40185405, DOI: 10.1016/j.jad.2025.03.198.Peer-Reviewed Original ResearchConceptsResponse to treatmentEsketamine treatmentFactors associated with response to treatmentRetrospective analysisMontgomery-Asberg Depression Rating ScaleNon-obese patientsTreatment-resistant depressionDepression Rating ScaleRetrospective analysis of real-world dataIncreased body fatIntranasal esketamineMontgomery-AsbergTreatment responseEsketaminePrimary outcomeActive metaboliteBMIBody fatPatientsTreating depressionRating ScaleContinuous variablesIntranasalTreatmentObesityProtein 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 interplayDisordersAltered hippocampal effective connectivity predicts BMI and food approach behavior in children with obesity
Li W, Chen X, Gao X, Pang Q, Guo C, Song S, Liu Y, Shi P, Chen H. Altered hippocampal effective connectivity predicts BMI and food approach behavior in children with obesity. International Journal Of Clinical And Health Psychology 2025, 25: 100541. PMID: 39877891, PMCID: PMC11773239, DOI: 10.1016/j.ijchp.2024.100541.Peer-Reviewed Original ResearchFood approach behaviorsApproach behaviorEffective connectivityPediatric obesityExcess weightEating behaviorsResting-state functional connectivityFood reward processingAssessment of eating behaviorModels of obesityLeft postcentral gyrusResting-state fMRIFollow-up assessmentReward processingNormal weightDynamic casual modelingHippocampal connectivityRight hippocampusPostcentral gyrusFunctional connectivityBMIAppetite regulationChildhood obesityAdult obesityObesity16 Metabolic Syndrome and Obesity
Alonso W, Canapari C. 16 Metabolic Syndrome and Obesity. 2025, 175-184. DOI: 10.1016/b978-0-323-75566-5.00016-2.Peer-Reviewed Original ResearchMetabolic syndromeComponents of metabolic syndromeInvolvement of adipocytokinesSleep-disordered breathingIncreased sympathetic activityElevated blood pressureCardiovascular risk factorsRates of obesityIntermittent hypoxemiaTruncal obesityDysregulation of glucose metabolismSleep fragmentationSympathetic activityBlood pressureSleep curtailmentRisk factorsSyndromeObesityShort sleepGlucose metabolismCircadian factorsSleepHypoxemiaDyslipidemiaAdipocytokinesDeterminants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals
Pesta D, Anadol-Schmitz E, Sarabhai T, Kamp Y, Gancheva S, Trinks N, Zaharia O, Mastrototaro L, Lyu K, Habets I, Kamp-Bruls Y, Dewidar B, Weiss J, Schrauwen-Hinderling V, Zhang D, Gaspar R, Strassburger K, Kupriyanova Y, Al-Hasani H, Szendroedi J, Schrauwen P, Phielix E, Shulman G, Roden M. Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals. Science Advances 2025, 11: eadr8849. PMID: 39742483, PMCID: PMC11691647, DOI: 10.1126/sciadv.adr8849.Peer-Reviewed Original ResearchConceptsOverweight-to-obeseNormal weightEndurance-trained humansMuscle mitochondrial contentAthlete's paradoxTrained athletesExercise-trainedOverweight individualsAthletesObesity subtypesObservational studyIntramyocellular triglyceride accumulationInsulin sensitivityHigher insulin sensitivityMitochondrial contentIncreased insulin sensitivityMuscleFemale individualsIndividualsInsulin resistanceObesityMitochondrial partitioningIncreased calpainNPKC activityProtein kinase C
2024
A meta‐analysis assessing reliability of the Yale Food Addiction Scale: Implications for compulsive eating and obesity
Jahrami H, Husain W, Trabelsi K, Ammar A, Pandi‐Perumal S, Saif Z, Potenza M, Lin C, Pakpour A. A meta‐analysis assessing reliability of the Yale Food Addiction Scale: Implications for compulsive eating and obesity. Obesity Reviews 2024, 26: e13881. PMID: 39715731, PMCID: PMC11884959, DOI: 10.1111/obr.13881.Peer-Reviewed Original ResearchConceptsYale Food Addiction ScaleRandom-effects meta-analysisReliability generalization meta-analysisMeta-analysisFood addictionTest-retest correlation coefficientTest-retest reliabilityComprehensive systematic reviewSixty-five studiesIntraclass coefficientSystematic reviewAddiction ScaleDisordered eatingCompulsive eatingObesitySample sizeEatingCorrelation coefficientEating disordersIntraclassReliability measuresReliabilityParticipantsScaleInceptionDaily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity
Barbieri E, Bonet J, Fox D, Nelson R, Nelson M, Nelson L, Fernandez C, Van Name M, Samuels S, Caprio S, Sabati M, Galderisi A, Sherr J, Man C, Santoro N. Daily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity. Obesity 2024, 33: 116-124. PMID: 39658509, PMCID: PMC11666407, DOI: 10.1002/oby.24175.Peer-Reviewed Original ResearchConceptsIntrahepatic fat contentDaily glucose variabilityLiver proton density fat fractionProton density fat fractionGlucose variabilityInsulin sensitivityOral glucose tolerance testFat fractionInsulin secretionAssociated with insulin resistanceFirst-phase insulin secretionAssociated with 2-h glucoseGlucose tolerance testGlucose standard deviationMagnetic resonance imagingOral minimal modelCoefficient of variationBasal insulin secretionPediatric obesityPostprandial glucoseTolerance testCell sensitivityInsulin resistanceObesityResonance imaging
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