Jens Bruning, MD
About
Biography
Dr. Jens Brüning is Director of the Max Planck Institute for Metabolism Research in Cologne and Director at the Policlinic for Endocrinology, Diabetes and Preventive Medicine at the University Hospital in Cologne. His research focusses on elucidating the CNS-dependent regulation of energy and glucose metabolism. These studies revealed a previously unappreciated role for insulin action in the central nervous system (CNS) to control organismal glucose homeostasis and insulin sensitivty. His group has defined distinct Agouti-related peptide (AgRP)-expressing neurons in the hypothalamus as critical mediators of insulin's metabolic actions, revealed the molecular mechanisms of insulin action in these neurons as well as their alterations in obesity. More recently, through the use of neurocircuitry mapping techniques his group defined the projections of these AgRP-neurons within the CNS, which govern insulin-dependent control of systemic insulin sensitivty via the regulation of autonomic innervation.
Education & Training
- MD
- University of Cologne (1993)
Research
Research at a Glance
Publications Timeline
Publications
2025
Author 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 ResearchCitationsAltmetricOrexin/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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMelanin-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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGenome-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 ResearchAltmetricConceptsExperimental 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 effectsAstrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
Ardanaz C, de la Cruz A, Minhas P, Hernández-Martín N, Pozo M, Valdecantos M, Valverde Á, Villa-Valverde P, Elizalde-Horcada M, Puerta E, Ramírez M, Ortega J, Urbiola A, Ederra C, Ariz M, Ortiz-de-Solórzano C, Fernández-Irigoyen J, Santamaría E, Karsenty G, Brüning J, Solas M. Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis. Science Advances 2024, 10: eadp1115. PMID: 39423276, PMCID: PMC11488540, DOI: 10.1126/sciadv.adp1115.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPeripheral glucose homeostasisBrain glucose metabolismGlucose metabolismAstrocytic glucose transporterGlucose homeostasisPeripheral glucose metabolismSystemic glucose metabolismATP releasePurinergic signalingBlood-borne glucoseBrain metabolismAstrocytesBrain energeticsInsulin signalingCognitive functionGlucose transportBrain functionMiceBrainGLUT1MetabolismHomeostasisObesityNPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation
Dodt S, Widdershooven N, Dreisow M, Weiher L, Steuernagel L, Wunderlich F, Brüning J, Fenselau H. NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation. Nature Communications 2024, 15: 5439. PMID: 38937485, PMCID: PMC11211344, DOI: 10.1038/s41467-024-49766-0.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsBed nucleus of the stria terminalisNPY-deficient miceBed nucleus of the stria terminalis neuronsGABAergic inputsControl of feeding behaviorPromote feedingAgRP neuronsOrexigenic neuropeptide Y (NPYSuppress food intakeNeuropeptide Y (NPYAmygdala circuitsAnxiety signalsExtended amygdalaCentral amygdalaBed nucleusCeA projectionsStria terminalisSynaptic adaptationDecreased anxietyAmygdalaSynaptic plasticityRelevant circuitsDecreased feedingAnxietyHypothalamic neuronsDevelopment of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release
Zhou X, Stine C, Prada P, Fusca D, Assoumou K, Dernic J, Bhat M, Achanta A, Johnson J, Pasqualini A, Jadhav S, Bauder C, Steuernagel L, Ravotto L, Benke D, Weber B, Suko A, Palmiter R, Stoeber M, Kloppenburg P, Brüning J, Bruchas M, Patriarchi T. Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release. Nature Communications 2024, 15: 5353. PMID: 38918403, PMCID: PMC11199706, DOI: 10.1038/s41467-024-49712-0.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOpioid peptide releaseVentral tegmental areaAcute brain slicesN/OFQ actionsChemogenetic activationIn vivo studiesNociceptin/orphanin FQTegmental areaFibre photometryOpioid peptidesBrain slicesPharmacological profileGenetically encoded sensorIntracellular signal transducersReceptor ligandsPeptide releaseMammalian brainFunctional relevanceNeuronsBehavioral processesSignal transducerReleasePotential interactionsRegulatory functionsN/OFQGABAergic disinhibition from the BNST to PNOCARC neurons promotes HFD-induced hyperphagia
Sotelo-Hitschfeld T, Minère M, Klemm P, Borgmann D, Wnuk-Lipinski D, Jais A, Jia X, Corneliussen S, Kloppenburg P, Fenselau H, Brüning J. GABAergic disinhibition from the BNST to PNOCARC neurons promotes HFD-induced hyperphagia. Cell Reports 2024, 43: 114343. PMID: 38865247, DOI: 10.1016/j.celrep.2024.114343.Peer-Reviewed Original ResearchCitationsAltmetricConceptsInhibition of POMC neuronsGamma-aminobutyric acidPOMC neuronsArcuate nucleusBed nucleus of the stria terminalisHFD feedingGABAergic disinhibitionAnorexic responseBed nucleusRabies tracingInhibitory inputsStria terminalisObesity developmentNeuronal activityNeuronal circuitsCircuit mappingNeuronsHyperphagiaHFDCaloric contentBNSTTerminalisObesityMicePOMCFood perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver
Henschke S, Nolte H, Magoley J, Kleele T, Brandt C, Hausen A, Wunderlich C, Bauder C, Aschauer P, Manley S, Langer T, Wunderlich F, Brüning J. Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver. Science 2024, 384: 438-446. PMID: 38662831, DOI: 10.1126/science.adk1005.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMitochondrial fragmentationInsulin-stimulated suppression of hepatic glucose productionInduced mitochondrial fragmentationMitochondrial fission factorPro-opiomelanocortin (POMC)-expressing neuronsControl of hepatic glucose metabolismKnock-in mutationHepatic glucose metabolismFission factorMitochondrial dynamicsSerine 131Fragments in vitroNutrient availabilityKnock-in miceMitochondrial functionDynamic regulationHepatic glucose productionLiver mitochondriaSuppression of hepatic glucose productionMetabolic adaptationPhosphorylationNutritional stateGlucose productionIn vivoGlucose metabolismSingle cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity
Leon S, Simon V, Lee T, Steuernagel L, Clark S, Biglari N, Lesté-Lasserre T, Dupuy N, Cannich A, Bellocchio L, Zizzari P, Allard C, Gonzales D, Le Feuvre Y, Lhuillier E, Brochard A, Nicolas J, Teillon J, Nikolski M, Marsicano G, Fioramonti X, Brüning J, Cota D, Quarta C. Single cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity. Nature Communications 2024, 15: 3443. PMID: 38658557, PMCID: PMC11043070, DOI: 10.1038/s41467-024-47877-2.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPOMC neuronsMouse models of obesityHypothalamic pro-opiomelanocortinAdult male miceDiet-induced obese miceModels of obesityReporter micePOMC expressionHypothalamic functionMale miceMature hypothalamusMouse modelDiversity of neuronsNeuronal diversityNeuronal identityObese micePro-opiomelanocortinSingle cell tracingNeuron numberPOMCMiceLineage tracingNeuronsWeight lossMetabolic output