Adjunct Faculty
Adjunct faculty typically have an academic or research appointment at another institution and contribute or collaborate with one or more School of Medicine faculty members or programs.
Adjunct rank detailsJens Bruning, MD
About
Research
Publications
2025
2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction
Kaul H, Isermann L, Senft K, Popovic M, Georgomanolis T, Baumann L, Sivanesan P, Pouikli A, Nolte H, Lucic B, Hildebrandt X, Seidel K, Gnad T, Gaedke F, Göbel U, Peters F, Cherevatenko M, Park J, Schauss A, Peltzer N, Brüning J, Kornfeld J, Pfeifer A, Langer T, Lusic M, Wickström S, Frezza C, Trifunovic A. 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction. Nature Metabolism 2025, 7: 1593-1613. PMID: 40750944, PMCID: PMC12373511, DOI: 10.1038/s42255-025-01332-8.Peer-Reviewed Original ResearchConceptsBrown adipose tissueNuclear stiffnessResponse to mitochondrial dysfunctionMitochondrial dysfunctionLipid droplet enlargementD-2HGAccumulation of lipid dropletsProtease ClpPFatty acid oxidationBrown adipocytesCellular homeostasisEpigenetic signaturesCellular metabolismGene expressionOncometabolite D-2-hydroxyglutarateD-2-hydroxyglutarateLipid dropletsMolecular underpinningsLipid accumulationExtrinsic cuesNuclear softeningAcid oxidationAdipose tissueClpPMitochondriaB 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. PMID: 40662198, PMCID: PMC12256348, 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 tissueHypothalamic 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 gainNPYNeurocircuitryAppetiteExpressionPNoCsMyeloperoxidase 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 formationReduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling
Zhu Y, Mehlkop O, Backes H, Cremer A, Porniece M, Klemm P, Steuernagel L, Chen W, Johnen R, Wunderlich F, Jais A, Brüning J. Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling. Cell Reports 2025, 44: 115522. PMID: 40186867, DOI: 10.1016/j.celrep.2025.115522.Peer-Reviewed Original ResearchConceptsShort-term HFD feedingNotch signalingIntracellular domainGlucose uptakeBrain microvascular endothelial cellsNotch intracellular domainHFD feedingDownregulation of Notch signalingHigh-fat dietBlood-brain barrierReduced Notch signalingGLUT1 expressionInsulin signalingSystemic insulin sensitivityBlood-brain barrier permeabilityNotch activationInduced expressionObesity-induced alterationsCaveolae formationPleiotropic effectsEndothelial cellsMicrovascular endothelial cellsExpressionBlood-brain barrier functionCultured brain microvascular endothelial cellsProjectome-based characterization of hypothalamic peptidergic neurons in male mice
Jiao Z, Gao T, Wang X, Wang A, Ma Y, Feng L, Gao L, Gou L, Zhang W, Biglari N, Boxer E, Steuernagel L, Ding X, Yu Z, Li M, Gao M, Hao M, Zhou H, Cao X, Li S, Jiang T, Qi J, Jia X, Feng Z, Ren B, Chen Y, Shi X, Wang D, Wang X, Han L, Liang Y, Qian L, Jin C, Huang J, Deng W, Wang C, Li E, Hu Y, Tao Z, Li H, Yu X, Xu M, Chang H, Zhang Y, Xu H, Yan J, Li A, Luo Q, Stoop R, Sternson S, Brüning J, Anderson D, Poo M, Sun Y, Xu S, Gong H, Sun Y, Xu X. Projectome-based characterization of hypothalamic peptidergic neurons in male mice. Nature Neuroscience 2025, 28: 1073-1088. PMID: 40140607, DOI: 10.1038/s41593-025-01919-0.Peer-Reviewed Original ResearchConceptsHypothalamic peptidergic neuronsMale micePeptidergic neuronsStructural basisInnate behaviorsHypothalamic functionBrain regionsPhysiological homeostasisAxonal projectionsCircuit mechanismsPeptidergic axonsHypothalamic axonsSoma distributionsHypothalamusMiceAxonsNeuropeptideTopographic organizationNeuronsMaleAuthor Correction: A comprehensive spatio-cellular map of the human hypothalamus
Tadross J, Steuernagel L, Dowsett G, Kentistou K, Lundh S, Porniece M, Klemm P, Rainbow K, Hvid H, Kania K, Polex-Wolf J, Knudsen L, Pyke C, Perry J, Lam B, Brüning J, Yeo G. Author Correction: A comprehensive spatio-cellular map of the human hypothalamus. Nature 2025, 639: e17-e17. PMID: 40000749, PMCID: PMC11903310, DOI: 10.1038/s41586-025-08826-1.Peer-Reviewed Original ResearchOrexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity
Izawa S, Fusca D, Jiang H, Heilinger C, Hausen A, Wunderlich F, Steuernagel L, Kloppenburg P, Brüning J. Orexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity. Cell Reports 2025, 44: 115277. PMID: 39946231, DOI: 10.1016/j.celrep.2025.115277.Peer-Reviewed Original ResearchConceptsMelanin-concentrating hormoneNon-rapid eye movementFemale miceInhibitory responsesREM sleepMelanin-Concentrating Hormone NeuronsInsulin sensitivityReceptor type 2Melanin-concentrating hormone neuron populationImpaired insulin sensitivityNeuronal sub-populationsOX2R expressionOrexin neuronsOrexin signalingSelective agonistsModulate sleepBrain slicesClinical trialsOX2RRegulate sleepNarcolepsy treatmentOrexinNeuronal populationsRNA expressionType 2A comprehensive spatio-cellular map of the human hypothalamus
Tadross J, Steuernagel L, Dowsett G, Kentistou K, Lundh S, Porniece M, Klemm P, Rainbow K, Hvid H, Kania K, Polex-Wolf J, Knudsen L, Pyke C, Perry J, Lam B, Brüning J, Yeo G. A comprehensive spatio-cellular map of the human hypothalamus. Nature 2025, 639: 708-716. PMID: 39910307, PMCID: PMC11922758, DOI: 10.1038/s41586-024-08504-8.Peer-Reviewed Original ResearchConceptsGenome-wide association study genesRare deleterious variantsHypothalamic cell typesCell typesSingle-nucleus sequencingBody mass indexTranscription mapDeleterious variantsNeuronal cell typesG protein-coupled receptorsStudy genesBiological functions1Spatial transcriptomicsTranscriptomic identityCellular componentsExpression levelsPro-opiomelanocortin neuronsHuman hypothalamusAssociated with body mass indexPopulation levelMetabolic disordersHypothalamic cellsExpressionNeuronal clustersTranscriptome
2024
Neuroprotective effect of neuron‐specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis
Amatruda M, Marechal D, Gacias M, Wentling M, Turpin‐Nolan S, Morstein J, Moniruzzaman M, Brüning J, Haughey N, Trauner D, Casaccia P. Neuroprotective effect of neuron‐specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis. Glia 2024, 73: 271-290. PMID: 39489703, PMCID: PMC11662985, DOI: 10.1002/glia.24631.Peer-Reviewed Original ResearchExperimental autoimmune encephalomyelitisNeuron-specific deletionMultiple sclerosisDemyelinating disordersCourse of EAESalvage pathwayAnimal model of multiple sclerosisModel of multiple sclerosisDisease severityRecycling of sphingosineWild type miceCeramide synthase 6Central nervous systemPalmitic acidAutoimmune encephalomyelitisExposure to oxidative stressType miceInflammatory demyelinationMyelin damageSaturated fatAnimal modelsMitochondrial dysfunctionCerS5Nervous systemNeuroprotective effects