2025
Hypothalamic 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 gainNPYNeurocircuitryAppetiteExpressionPNoCsImpact of high temperatures on enzyme-linked immunoassay (ELISA) performance for leptin measurements in human milk stored under varied freeze/thaw conditions
Bertacchi V, Corley M, Aronsen G, Bribiescas R. Impact of high temperatures on enzyme-linked immunoassay (ELISA) performance for leptin measurements in human milk stored under varied freeze/thaw conditions. PLOS ONE 2025, 20: e0320366. PMID: 40106448, PMCID: PMC11957766, DOI: 10.1371/journal.pone.0320366.Peer-Reviewed Original ResearchConceptsMilk samplesHigh ambient temperature exposureExposure to warm temperaturesWarmer temperaturesHuman milk samplesImpact of high temperatureNormal kitsRecommended temperatureAssay performance validationEnzyme-linked immunoassayAmbient temperature exposureAmbient temperature conditionsHigh temperatureTemperature conditionsELISA kitsTemperature exposureLeptin measurementsShipping conditionsLaboratory analysis
2024
The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood
Jia Z, Qiu F, He Y, Chen H, Yang C, Liu H, Zheng T, Xu S, Wang S, Li Y. The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood. BMC Medicine 2024, 22: 429. PMID: 39379967, PMCID: PMC11462715, DOI: 10.1186/s12916-024-03629-z.Peer-Reviewed Original ResearchConceptsRestricted cubic splinesLeptin levelsMetabolic hormonesMetabolic healthDNA methylationRestricted cubic spline analysisProspective birth cohort studyDNA methylation ageMother-child pairsBirth cohort studyDNA copy numberFetal originMitochondrial DNA copy numberResultsThe linear regression analysisReal-time PCRCohort studyHorvath's epigenetic clockInsulin levelsInverse associationLeptinQuantitative real-time PCRInfinium MethylationEPIC BeadChipElectrochemiluminescence assayLinear regression analysisMetabolic statusHypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation
Mohr S, Dai Pra R, Platt M, Feketa V, Shanabrough M, Varela L, Kristant A, Cao H, Merriman D, Horvath T, Bagriantsev S, Gracheva E. Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation. Nature Communications 2024, 15: 5803. PMID: 38987241, PMCID: PMC11236985, DOI: 10.1038/s41467-024-49996-2.Peer-Reviewed Original ResearchConceptsHypothalamic feeding centersHormone deficiencyHypothalamic arcuate nucleus neuronsArcuate nucleus neuronsThyroid hormone deficiencyFeeding centerEffects of ghrelinAnorexigenic effectNucleus neuronsPhysiological anorexiaThyroid hormonesNormal physiological functionsGround squirrelsInterbout arousalAnorexiaThirteen-lined ground squirrelsProlonged periodReduced sensitivityPhysiological functionsDeficiencyThe milk study protocol: A longitudinal, prospective cohort study of the relationship between human milk metabolic hormone concentration, maternal body composition, and early growth and satiety development in Samoan infants aged 1–4 months
Harries V, Abraham J, Vesi L, Reupena A, Faaselele-Savusa K, Duckham R, Bribiescas R, Hawley N. The milk study protocol: A longitudinal, prospective cohort study of the relationship between human milk metabolic hormone concentration, maternal body composition, and early growth and satiety development in Samoan infants aged 1–4 months. PLOS ONE 2024, 19: e0292997. PMID: 38728264, PMCID: PMC11086876, DOI: 10.1371/journal.pone.0292997.Peer-Reviewed Original ResearchConceptsMaternal body compositionEarly infant growthBody compositionInfant growthProspective longitudinal cohortMother-infant dyadsBreastfeeding mother-infant dyadsHuman milkFingerpick blood sampleInfants aged 1Longitudinal cohortBody composition measurementsProspective cohort studyInfant feeding patternsSatiety developmentUndernourished womenSatiety responsivenessInfant satietyInfant hungerHormone leptinCohort studyHigh-income settingsMultivariate analysisEating patternsHormone transfer
2023
Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis
Ozmen A, Nwabuobi C, Tang Z, Guo X, Larsen K, Guller S, Blas J, Moore M, Kayisli U, Lockwood C, Guzeloglu-Kayisli O. Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis. International Journal Of Molecular Sciences 2023, 25: 135. PMID: 38203306, PMCID: PMC10778808, DOI: 10.3390/ijms25010135.Peer-Reviewed Original ResearchConceptsIL-6 expressionHofbauer cellsP65 NF-κBIL-6NF-κBLeptin levelsPreeclampsia pathogenesisElevated serum interleukin-6 levelsSerum interleukin-6 levelsERK1/2 MAPKInterleukin-6 levelsPro-inflammatory phenotypeAnti-inflammatory phenotypeLeptin receptor expressionIL-6 productionPathogenesis of PEPlacental leptin productionPhosphorylation levelsERK1/2 MAPK inhibitorIL-6 regulationConcentration-dependent mannerPE patientsHuman pregnancySecond trimesterLeptin concentrationsA chromosome-level genome assembly for the Silkie chicken resolves complete sequences for key chicken metabolic, reproductive, and immunity genes
Zhu F, Yin Z, Zhao Q, Sun Y, Jie Y, Smith J, Yang Y, Burt D, Hincke M, Zhang Z, Yuan M, Kaufman J, Sun C, Li J, Shao L, Yang N, Hou Z. A chromosome-level genome assembly for the Silkie chicken resolves complete sequences for key chicken metabolic, reproductive, and immunity genes. Communications Biology 2023, 6: 1233. PMID: 38057566, PMCID: PMC10700341, DOI: 10.1038/s42003-023-05619-y.Peer-Reviewed Original ResearchConceptsGenome assemblyReference genomeChromosome-level reference genomeChromosome-level genome assemblyGenetic variation mapResponse to pathogen challengeComplex genetic regionWhole-genome methylationImmunologically important genesDifferentially regulated genesPan-genomeGenome sequenceGenetic regionsGenomic studiesImportant genesOvocleidin-17Pathogen challengeSilky chickenGenetic foundationImmune genesGenomeFunctional validationGenesFibromelanosisSilkyPreclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency
Altarejos J, Pangilinan J, Podgrabinska S, Akinci B, Foss-Freitas M, Neidert A, Ray Y, Zheng W, Kim S, Kamat V, Huang M, Min S, Mastaitis J, Dominguez-Gutierrez G, Kim J, Stevis P, Huang T, Zambrowicz B, Olson W, Godin S, Bradley E, Gewitz A, Baker M, Hench R, Davenport M, Chenevert T, DiPaola F, Yancopoulos G, Murphy A, Herman G, Musser B, Dansky H, Harp J, Gromada J, Sleeman M, Oral E, Olenchock B. Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency. Science Translational Medicine 2023, 15: eadd4897. PMID: 37992152, DOI: 10.1126/scitranslmed.add4897.Peer-Reviewed Original ResearchConceptsLeptin concentrationsBody weightHepatic steatosisAdipose-derived hormone leptinClass 3 obesityCompassionate use treatmentHigher baseline leptinLeptin knockout miceAcceptable safety profileLower leptin concentrationsPresence of leptinHuman monoclonal antibodyLeptin receptor signalingTreatment of individualsPhase 1Baseline leptinLepr signalingLeptin deficiencyMetabolic sequelaeLiver diseaseClinical benefitSafety profileInsulin resistanceBlood glucoseInsulin sensitivityFunctional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar
Mohammed I, Selvaraj S, Ahmed W, Al-Barazenji T, Hammad A, Dauleh H, Saraiva L, Al-Shafai M, Hussain K. Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar. International Journal Of Molecular Sciences 2023, 24: 16361. PMID: 38003551, PMCID: PMC10671262, DOI: 10.3390/ijms242216361.Peer-Reviewed Original ResearchConceptsCREB signaling pathwaysHeterozygous variantsSignaling pathwayVariants associated with obesityIn silico prediction toolsEffects of allelic variationFunctional impactIn silico analysisMonogenic obesityDownstream signaling cascadesLigand binding activityGT1-7 cellsObesity-related genesIdentified variantsAllelic variationFunctional characterizationSilico analysisSanger sequencingPathogenic variantsActivation of PKALeptin-melanocortin pathwaySignaling cascadesMonogenic forms of obesityGenesIn vitro analysisPlasma concentration of leptin is related to food addiction in gambling disorder: Clinical and neuropsychological implications
Etxandi M, Baenas I, Mora-Maltas B, Granero R, Fernández-Aranda F, Tovar S, Solé-Morata N, Lucas I, Casado S, Gómez-Peña M, Moragas L, del Pino-Gutiérrez A, Tapia J, Valenciano-Mendoza E, Potenza M, Gearhardt A, Diéguez C, Jiménez-Murcia S. Plasma concentration of leptin is related to food addiction in gambling disorder: Clinical and neuropsychological implications. Journal Of Behavioral Addictions 2023, 12: 1019-1031. PMID: 38141066, PMCID: PMC10786224, DOI: 10.1556/2006.2023.00051.Peer-Reviewed Original ResearchConceptsBody mass indexLeptin concentrationsFood addictionPlasma concentrationsHigher Body Mass IndexAppetite-regulating hormonesYale Food Addiction Scale 2.0Gambling disorderSemi-structured clinical interviewLiver-expressed antimicrobial peptide 2Clinical featuresMass indexAppetite regulationHormonal variablesBlood samplesLifetime diagnosisPatientsAntimicrobial peptide 2Clinical InterviewNeuropsychological featuresPoor inhibitory controlAnthropometric variablesEndocrine measuresHormonal concentrationsLeptinThe lncOb rs10487505 polymorphism impairs insulin sensitivity and glucose tolerance in children and adolescents with obesity
Umano G, Cirillo G, Sanchez G, Rondinelli G, Foderini M, Ferrara S, Di Sessa A, Marzuillo P, Papparella A, Santoro N, del Giudice E. The lncOb rs10487505 polymorphism impairs insulin sensitivity and glucose tolerance in children and adolescents with obesity. Obesity 2023, 31: 2359-2364. PMID: 37550829, DOI: 10.1002/oby.23835.Peer-Reviewed Original ResearchConceptsHomeostasis model assessmentInsulin resistanceDisposition indexLower whole-body insulin sensitivity indexModel assessmentWhole-body insulin sensitivity indexRisk of prediabetesHigher fasting insulinLower disposition indexPlasma leptin levelsInsulin sensitivity indexBMI z-scoreLeptin plasma levelsLeptin gene transcriptionFasting insulinGlucose toleranceLeptin levelsCC patientsRetrospective studyPlasma levelsAnthropometrical evaluationInsulin sensitivityHormone levelsHigh prevalenceHigh riskRandomized trial of exercise on cancer‐related blood biomarkers and survival in women with ovarian cancer
Cartmel B, Li F, Zhou Y, Gottlieb L, Lu L, Mszar R, Harrigan M, Ligibel J, Gogoi R, Schwartz P, Risch H, Irwin M. Randomized trial of exercise on cancer‐related blood biomarkers and survival in women with ovarian cancer. Cancer Medicine 2023, 12: 15492-15503. PMID: 37269192, PMCID: PMC10417064, DOI: 10.1002/cam4.6187.Peer-Reviewed Original ResearchConceptsExercise interventionOvarian cancerTrial of exerciseExercise-induced changesMin/weekGroup differencesSubset of participantsCause mortalityExercise groupOverall survivalStudy armsCA 125Randomized trialsBlood biomarkersBlood drawBreast cancerClinical significanceIGF-1Effect model analysisSecondary analysisBeneficial effectsCancerBiomarkersTrialsWomenMale Runners With Lower Energy Availability Have Impaired Skeletal Integrity Compared to Nonathletes
Haines M, Kaur S, Scarff G, Lauze M, Gerweck A, Slattery M, Oreskovic N, Ackerman K, Tenforde A, Popp K, Bouxsein M, Miller K, Misra M. Male Runners With Lower Energy Availability Have Impaired Skeletal Integrity Compared to Nonathletes. The Journal Of Clinical Endocrinology & Metabolism 2023, 108: e1063-e1073. PMID: 37079740, PMCID: PMC10505543, DOI: 10.1210/clinem/dgad215.Peer-Reviewed Original ResearchConceptsBone mineral densityImpaired skeletal integrityMale runnersLean massCalcium intakeCaloric intakeRunning mileageSkeletal integrityBone mineral density Z-scoreLumbar spine BMD Z-scoreBSI riskTrabecular volumetric bone mineral densityImpaired bone mineral densitySpine BMD Z-scoreZ-scoreVolumetric bone mineral densityTibial failure loadBMD Z-scoresExercise energy expenditureInsufficient caloric intakeAppendicular lean massWeight-bearing activitiesBody mass indexTrabecular bone volume fractionEnergy expenditure
2022
Effects of the Seed Oil of Carica papaya Linn on Food Consumption, Adiposity, Metabolic and Inflammatory Profile of Mice Using Hyperlipidic Diet
Santana L, do Espirito Santo B, Tatara M, Negrão F, Croda J, Alves F, de Oliveira Filiú W, Cavalheiro L, Nazário C, Asato M, de Faria B, do Nascimento V, de Cássia Avellaneda Guimarães R, de Cássia Freitas K, Hiane P. Effects of the Seed Oil of Carica papaya Linn on Food Consumption, Adiposity, Metabolic and Inflammatory Profile of Mice Using Hyperlipidic Diet. Molecules 2022, 27: 6705. PMID: 36235241, PMCID: PMC9570947, DOI: 10.3390/molecules27196705.Peer-Reviewed Original ResearchConceptsOral glucose toleranceHigh-fat dietArea of adipocytesInsulin sensitivity testAcute toxicity testInflammatory profileGlucose toleranceTotal cholesterolFatty acidsIL-6Insulin resistanceMCP-1Swiss miceHyperlipidic dietLower insulinCaloric intakeMonounsaturated fatty acidsProtective effectHypoglycemic effectAdipose tissueCytokine resistanceWeight gainAdiposityFood consumptionFatty acid compositionTET3 epigenetically controls feeding and stress response behaviors via AGRP neurons
Xie D, Stutz B, Li F, Chen F, Lv H, Sestan-Pesa M, Catarino J, Gu J, Zhao H, Stoddard CE, Carmichael GG, Shanabrough M, Taylor HS, Liu ZW, Gao XB, Horvath TL, Huang Y. TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons. Journal Of Clinical Investigation 2022, 132: e162365. PMID: 36189793, PMCID: PMC9525119, DOI: 10.1172/jci162365.Peer-Reviewed Original ResearchConceptsAgRP neuronsNeuropeptide YExpression of AgRPControl of feedingHypothalamic agoutiAnxiolytic effectsNeurotransmitter GABAMouse modelLeptin signalingStress-like behaviorsGenetic ablationNeuronsAgRPCritical central regulatorsEnergy expenditureGABAEnergy metabolismAppetiteFeedingCentral regulatorMetabolismCentral controlHuman cellsTET3ObesityRace-specific associations of urinary phenols and parabens with adipokines in midlife women: The Study of Women's Health Across the Nation (SWAN)
Lee S, Karvonen-Gutierrez C, Mukherjee B, Herman W, Park S. Race-specific associations of urinary phenols and parabens with adipokines in midlife women: The Study of Women's Health Across the Nation (SWAN). Environmental Pollution 2022, 303: 119164. PMID: 35306088, PMCID: PMC9883839, DOI: 10.1016/j.envpol.2022.119164.Peer-Reviewed Original ResearchConceptsStudy of Women's HealthBayesian kernel machine regressionWomen's healthLeptin levelsBlack womenAssociated with lower leptinAssociated with favorable profilesAsian womenSoluble leptin receptorRacial differencesRace-specific associationsUrinary phenolCross-sectional associationsNo significant associationObesity-related metabolic diseasesLog-transformed levelsSOB-RKernel machine regressionSerum adipokinesMetabolic disease burdenEffect modificationNation Multi-Pollutant StudyLow leptinLeptin receptorLinear regression models
2021
Replicability of leptin associations with testosterone, estradiol, follicle‐stimulating hormone, and luteinizing hormone in healthy Ache men of Paraguay: A multiple daily assessment
Harries V, Bribiescas R. Replicability of leptin associations with testosterone, estradiol, follicle‐stimulating hormone, and luteinizing hormone in healthy Ache men of Paraguay: A multiple daily assessment. American Journal Of Human Biology 2021, 34: e23638. PMID: 34213036, DOI: 10.1002/ajhb.23638.Peer-Reviewed Original ResearchConceptsFollicle-stimulating hormoneLeptin's associationsMale reproductive hormone levelsSerum follicle-stimulating hormoneMale reproductive hormonesReproductive hormone levelsMultiple daily assessmentsLeptin levelsEstradiol levelsHealthy menHormone levelsReproductive hormonesLeptinSeparate daysTestosteroneDaily assessmentHormoneSmall sample sizeAche menSalivary testosteroneMenLifestyle variationsSpan of daysEstradiolLHObesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension
Gruber T, Pan C, Contreras RE, Wiedemann T, Morgan DA, Skowronski AA, Lefort S, De Bernardis Murat C, Le Thuc O, Legutko B, Ruiz-Ojeda FJ, de la Fuente-Fernández M, García-Villalón AL, González-Hedström D, Huber M, Szigeti-Buck K, Müller TD, Ussar S, Pfluger P, Woods SC, Ertürk A, LeDuc CA, Rahmouni K, Granado M, Horvath TL, Tschöp MH, García-Cáceres C. Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension. Cell Metabolism 2021, 33: 1155-1170.e10. PMID: 33951475, PMCID: PMC8183500, DOI: 10.1016/j.cmet.2021.04.007.Peer-Reviewed Original ResearchConceptsBlood pressureObesity-associated increaseObesity-induced hypertensionElevated blood pressureSystemic blood pressureEndothelial growth factorHIF1α-VEGFArterial hypertensionNovel mechanistic linkSympathetic hyperactivityHemodynamic homeostasisHypothalamic astrocytesMetabolic syndromeRegion-specific lossMacrovascular systemsLeptin signalingBrain centersPathophysiological processesHypertensionGliovascular interfacePathway disruptionGrowth factorAstrocytesMechanistic linkAngiopathyDefective autophagy in Sf1 neurons perturbs the metabolic response to fasting and causes mitochondrial dysfunction
Coupé B, Leloup C, Asiedu K, Maillard J, Pénicaud L, Horvath TL, Bouret SG. Defective autophagy in Sf1 neurons perturbs the metabolic response to fasting and causes mitochondrial dysfunction. Molecular Metabolism 2021, 47: 101186. PMID: 33571700, PMCID: PMC7907893, DOI: 10.1016/j.molmet.2021.101186.Peer-Reviewed Original ResearchConceptsLoss of Atg7Energy homeostasisCellular homeostasisGene Atg7Defective autophagyMitochondria morphologyPhysiological processesCellular responsesCellular componentsMetabolic responseMitochondrial dysfunctionAutophagyAtg7SF1 neuronsHomeostasisMutant miceNeurons displayLoxP/Energy expenditure regulationImportant roleVMH neuronsVentromedial nucleusLeptin sensitivityStarvationCentral response
2020
Urinary metals and adipokines in midlife women: The Study of Women's Health Across the nation (SWAN)
Wang X, Karvonen-Gutierrez C, Mukherjee B, Herman W, Park S. Urinary metals and adipokines in midlife women: The Study of Women's Health Across the nation (SWAN). Environmental Research 2020, 196: 110426. PMID: 33157106, PMCID: PMC8093324, DOI: 10.1016/j.envres.2020.110426.Peer-Reviewed Original ResearchConceptsStudy of Women's HealthWomen's healthExposure to cadmiumUrinary metal concentrationsUrinary molybdenumMetal concentrationsMetal exposureSOB-RUrinary metalsNation Multi-Pollutant StudyAssociated with favorable profilesStandard deviation increaseCadmiumLinear regression modelsAdverse adipokine profileMidlife womenLevels of sOB-RHMW adiponectinUrinary cesiumFollow-up visitHuman populationSoluble leptin receptorAdaptive elastic-netSOB-R levelsMetal
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