ArticleCell metabolism2021
Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension.
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Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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68citing papers in PubMed, 1 pooled it
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- The Impact of Bariatric Surgery Versus Non-Surgical Treatment on Blood Pressure: Systematic Review and Meta-Analysis.Obesity surgery · 2021Pooled it
- Effects of obesity on brain health and cognition.Nature reviews. Neurology · 2026Review
- Hypothalamic neurovascular and extracellular matrix remodeling: Cellular niche orchestration of immune-metabolic adaptation to nutritional stress.Reviews in endocrine & metabolic disorders · 2026Review
- Acute anti-obesity treatment with celastrol reduces body weight, cerebral inflammation and metabolic imbalances in mice.Molecular medicine (Cambridge, Mass.) · 2026Article
- Neurovascular plasticity as a modulator of hypothalamic function.Reviews in endocrine & metabolic disorders · 2026Review
- Hypothalamic regulation of energy homeostasis: Quo vadis.Reviews in endocrine & metabolic disorders · 2026Review
- The neuro-vascular-immune triad: the interactive network in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Obesity as a catalyst for neurodegeneration.Nature metabolism · 2026Review
- Trunk-to-Appendicular Fat Ratio and Blood Pressure: Survey-Weighted Regression, Spline Modeling, and Exploratory Lipid Attenuation Analysis.International journal of hypertension · 2026Article
- Emerging roles of astrocytes in autonomic control of blood pressure and hypertension.American journal of physiology. Cell physiology · 2025Review
- Fundamental role of brain-organ interaction in behavior-driven holistic homeostasis.Fundamental research · 2025Review
- Bone Mineral Accrual From Adolescence Into Young Adulthood and Peak Bone Mass: A Longitudinal Cohort Study.Health science reports · 2025Article
- Case report: Metreleptin rapidly improved anorexia nervosa related and comorbid psychopathology in a patient with high endogenous leptin levels adjusted for body mass index.European child & adolescent psychiatry · 2025Article
- Glial fibrillary acidic protein vs. S100B to identify astrocytes impacted by sex and high fat diet.Physiology & behavior · 2025Article
- The Hidden Price of Plenty: Oxidative Stress and Calorie-Induced Cardiometabolic Dysfunction.Life (Basel, Switzerland) · 2025Review
- Hypothalamic Gliosis Is Associated With Multiple Cardiovascular Disease Risk Factors in the Framingham Heart Study.Journal of the American Heart Association · 2025Article
- Brain-Targeted Reactive Oxygen Species in Hypertension: Unveiling Subcellular Dynamics, Immune Cross-Talk, and Novel Therapeutic Pathways.Antioxidants (Basel, Switzerland) · 2025Review
- Large Scale in vivo Acquisition, Segmentation and 3D Reconstruction of Cortical Vasculature usingNeuroinformatics · 2025Article
- Update on Hypothalamic Inflammation and Gliosis: Expanding Evidence of Relevance Beyond Obesity.Current obesity reports · 2025Review
- Correlation Between Blood Pressure Variability and Serum Vascular Endothelial Growth Factor Concentration in Patients with Type I Cerebral Small Vessel Disease.International journal of general medicine · 2025Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 11 institutions in 3 countries.
Tim GruberInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Institute for Advanced Studies, Technische Universität, 85748 Garching, Germany.
Chenchen PanInstitute for Tissue Engineering and Regenerative Medicine (ITERM), Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
Raian E ContrerasInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Research Unit Neurobiology of Diabetes, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Neurobiology of Diabetes, TUM School of Medicine, Technical University Munich, 80333 Munich, Germany.
Tobias WiedemannInstitute for Diabetes and Cancer, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany.
Donald A MorganDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, USA.
Alicja A SkowronskiDivision of Molecular Genetics, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY, USA.
Sandrine LefortInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Cahuê De Bernardis MuratInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Ophelia Le ThucInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Beata LegutkoInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Francisco J Ruiz-OjedaGerman Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; RG Adipocytes & Metabolism, Institute for Diabetes & Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
María de la Fuente-FernándezPhysiology Department, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Angel Luis García-VillalónPhysiology Department, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Daniel González-HedströmPhysiology Department, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Melanie HuberInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Klara Szigeti-BuckProgram in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Timo D MüllerInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany.
Siegfried UssarGerman Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; RG Adipocytes & Metabolism, Institute for Diabetes & Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany; Department of Medicine, Technische Universität, Munich, Germany.
Paul PflugerInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Research Unit Neurobiology of Diabetes, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Neurobiology of Diabetes, TUM School of Medicine, Technical University Munich, 80333 Munich, Germany.
Steve C WoodsDepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
Ali ErtürkInstitute for Tissue Engineering and Regenerative Medicine (ITERM), Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
Charles A LeDucDivision of Molecular Genetics, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY, USA.
Kamal RahmouniDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, USA.
Miriam GranadoPhysiology Department, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Tamas L HorvathInstitute for Advanced Studies, Technische Universität, 85748 Garching, Germany; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Matthias H TschöpInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Division of Metabolic Diseases, Department of Medicine, Technische Universität, Munich, Germany. Electronic address: matthias.tschoep@helmholtz-muenchen.de.
Cristina García-CáceresInstitute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Medizinische Klinik and Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address: garcia-caceres@helmholtz-muenchen.de.
Deutsches Diabetes-Zentrum e.V. · DEHelmholtz Zentrum München · DEUniversidad Autónoma de Madrid · ESTechnical University of Munich · DEColumbia University · USUniversity of Iowa · USYale University · USGerman Center for Diabetes Research · DEHeinrich Heine University Düsseldorf · DELudwig-Maximilians-Universität München · DEUniversity of Cincinnati · US
Funding
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0MRole of the brain Renin-Angiotensin Sys. in Cardiovas and Metabolic RegulationP01HL084207 · NHLBI · UNIVERSITY OF IOWA · PI GROBE, JUSTIN L · 2007 to 2022
$30.2MPOSTDOCTORAL TRAINING IN ARTERIOSCLEROSIS RESEARCHT32HL007343 · NHLBI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI HENRY N GINSBERG, Muredach P Reilly · 1985 to 2026
$12.7MNeuronal Mechanisms of Obesity-Induced HypertensionI01BX004249 · VA · IOWA CITY VA MEDICAL CENTER · PI KAMAL RAHMOUNI · 2019 to 2026
–BLRD VA I01 BX004249NCATS NIH HHS UL1 TR001873NHLBI NIH HHS P01 HL084207NHLBI NIH HHS T32 HL007343
Abstract
Pathologies of the micro- and macrovascular systems are a hallmark of the metabolic syndrome, which can lead to chronically elevated blood pressure. However, the underlying pathomechanisms involved still need to be clarified. Here, we report that an obesity-associated increase in serum leptin triggers the select expansion of the micro-angioarchitecture in pre-autonomic brain centers that regulate hemodynamic homeostasis. By using a series of cell- and region-specific loss- and gain-of-function models, we show that this pathophysiological process depends on hypothalamic astroglial hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling downstream of leptin signaling. Importantly, several distinct models of HIF1α-VEGF pathway disruption in astrocytes are protected not only from obesity-induced hypothalamic angiopathy but also from sympathetic hyperactivity or arterial hypertension. These results suggest that hyperleptinemia promotes obesity-induced hypertension via a HIF1α-VEGF signaling cascade in hypothalamic astrocytes while establishing a novel mechanistic link that connects hypothalamic micro-angioarchitecture with control over systemic blood pressure.
Indexed as
AnimalsAstrocytesFemaleHypertensionHypothalamusLeptinMaleMiceMice, Inbred C57BLObesityLeptinangiogenesisastrocytesHIF1α-VEGFhypertensionhypothalamusleptinobesity
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