Jens Bruning, MD
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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
Publications
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 outputDepletion of TBC1D4 Improves the Metabolic Exercise Response by Overcoming Genetically Induced Peripheral Insulin Resistance.
Springer C, Binsch C, Weide D, Toska L, Cremer A, Backes H, Scheel A, Espelage L, Kotzka J, Sill S, Kurowski A, Kim D, Karpinski S, Schnurr T, Hansen T, Hartwig S, Lehr S, Cames S, Brüning J, Lienhard M, Herwig R, Börno S, Timmermann B, Al-Hasani H, Chadt A. Depletion of TBC1D4 Improves the Metabolic Exercise Response by Overcoming Genetically Induced Peripheral Insulin Resistance. Diabetes 2024, 73: 1058-1071. PMID: 38608276, DOI: 10.2337/db23-0463.Peer-Reviewed Original ResearchCitationsAltmetricConceptsWhite adipose tissueLoss-of-function variantsAnalysis of glucose uptakeRegulation of glucose transportInterscapular brown adipose tissueHigh-fat dietEnhanced expression levelsDevelopment of insulin resistanceBrown adipose tissueMitochondrial activityTBC1D4Gene variantsInsulin resistanceAdipose tissueGlucose uptakePeripheral insulin resistanceGlucose transportExpression levelsGenesPrecision medicineInsulin toleranceGeneticsIncreased glucose clearanceExercise responseIn vivoActivation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor
Engström Ruud L, Font-Gironès F, Zajdel J, Kern L, Teixidor-Deulofeu J, Mannerås-Holm L, Carreras A, Becattini B, Björefeldt A, Hanse E, Fenselau H, Solinas G, Brüning J, Wunderlich T, Bäckhed F, Ruud J. Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor. Cell Reports 2024, 43: 113960. PMID: 38507407, DOI: 10.1016/j.celrep.2024.113960.Peer-Reviewed Original ResearchConceptsGlucose to lipid oxidationMetabolomics analysis of bloodImpaired insulin sensitivityRelease of stress hormonesAdipose tissue differentiationAnalysis of bloodGlucose uptakeVisceral fatChronic activationAcute activationGlucose toleranceMetabolomic analysisTranscriptome of muscleObesity treatmentTorpor-like stateNeuronal activityCell-specific activityInsulin sensitivityNauseaMetformin effectsHypothermiaWeight lossNeuronsEnergy homeostasisAugmented glucose uptakeReciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism
De Solis A, Del Río-Martín A, Radermacher J, Chen W, Steuernagel L, Bauder C, Eggersmann F, Morgan D, Cremer A, Sué M, Germer M, Kukat C, Vollmar S, Backes H, Rahmouni K, Kloppenburg P, Brüning J. Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism. Nature Metabolism 2024, 6: 473-493. PMID: 38378998, PMCID: PMC10963273, DOI: 10.1038/s42255-024-00987-z.Peer-Reviewed Original ResearchCitationsAltmetricConceptsInhibition of POMC neuronsPOMC neuronsFood intakeAgRP neuronsEffects of Agrp neuron activationActivation of AgRP neuronsActivating AgRP neuronsActivation of AgRPInhibit POMC neuronsProopiomelanocortin (POMC)-expressing neuronsAgRP neuron activityNucleus tractus solitariiRegulate food intakePromote food consumptionSystemic insulin sensitivityControl of feedingParaventricular nucleusTractus solitariiNeuronal inhibitionTH+ neuronsFemale miceChemogenetic receptorsNeuronal activityAgRPInsulin sensitivity