ArticleCell metabolism2022
Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders.
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Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
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14 citing papers in PubMed, 39 citations in OpenAlex.
- Beyond satiety: unraveling the complex roles of POMC neurons in behavior and metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Metabolomic Pathways Distinguishing Metabolically Healthy and Unhealthy Obesity from Normal-Weight: A Cross-Sectional Study.International journal of molecular sciences · 2026Article
- Effects of Repeated Early-life Anesthesia Exposure on Visual System Development in Mice.Anesthesiology · 2026Article
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- Intestinal Clock Promotes Cognitive Memory Through Adenosine Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neurosteroids: a lifelong impact on brain health.Frontiers in behavioral neuroscience · 2025Review
- Functional Food Nutrients, Redox Resilience Signaling and Neurosteroids for Brain Health.International journal of molecular sciences · 2024Review
- The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice.Journal of neuroinflammation · 2023Article
- ER-mitochondria contacts and cholesterol metabolism are disrupted by disease-associated tau protein.EMBO reports · 2023Article
- Alcohol and pregnenolone interaction on cerebral arteries through targeting of vascular smooth muscleAdvances in drug and alcohol research · 2023Article
- Neurosteroids and early-life programming: An updated perspective.Current opinion in endocrine and metabolic research · 2022Article
- Sex differences and the lack of effects of chemogenetic manipulation of pro-opiomelanocortin (POMC) neurons on alcohol consumption in male and female mice.Brain research · 2022Article
- The results of a unique dietary supplement (nutraceutical formulation) used to treat the symptoms of long-haul COVID.Frontiers in nutrition · 2022Article
- Relevance of sex-differenced analyses in bioenergetics and nutritional studies.Frontiers in nutrition · 2022Article
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Authors and funding
29 authors at 11 institutions in 4 countries.
Sara RamírezNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: ramirez@clinic.cat.
Roberta Haddad-TóvolliNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Marija RadosevicNeuroimmunology Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
Miriam ToledoNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Adriana PanéObesity Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
Daniel AlcoleaMemory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Vicent RibasDepartment of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
Maria Milà-GuaschNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Macarena PozoNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Arnaud ObriNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Elena EyreNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Alicia G Gómez-ValadésNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Iñigo ChiviteNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Tomas Van EeckhoutNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Ioannis ZalachorasLaboratory of Behavioral Genetics, Brain Mind Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Jordi AltirribaLaboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Corinna BauderDepartment of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
Mónica ImbernónDepartment of Physiology, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), University of Santiago de Compostela, Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.
Gloria GarrabouMuscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Internal Medicine Department, Faculty of Medicine, University of Barcelona, Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
Carmen Garcia-RuizDepartment of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain; Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Rubén NogueirasDepartment of Physiology, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), University of Santiago de Compostela, Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain.
David SotoNeurophysiology Laboratory, Department of Biomedicine, Faculty of Medicine, Neuroscience Institute, University of Barcelona, Barcelona, Spain.
Xavier GasullNeurophysiology Laboratory, Department of Biomedicine, Faculty of Medicine, Neuroscience Institute, University of Barcelona, Barcelona, Spain.
Carmen SandiLaboratory of Behavioral Genetics, Brain Mind Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Jens C BrüningDepartment of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; National Center for Diabetes Research (DZD), Neuherberg, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEPD), University Hospital of Cologne, Cologne, Germany.
Juan ForteaMemory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain; Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain.
Amanda JiménezObesity Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain; Translational Research in Diabetes, Lipids and Obesity, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
José C Fernández-ChecaDepartment of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain; Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Marc ClaretNeuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Faculty of Medicine, Universitat de Barcelona, Barcelona, Spain. Electronic address: mclaret@clinic.cat.
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESHospital Clínic de Barcelona · ESUniversitat de Barcelona · ESBiomedical Research Networking Center on Neurodegenerative Diseases · ESÉcole Polytechnique Fédérale de Lausanne · CHCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESInstituto de Investigación Sanitaria de Santiago · ESMax Planck Institute for Metabolism Research · DEUniversidade de Santiago de Compostela · ESUniversity Hospital Cologne · DEUniversity of Geneva · CH
Funding
The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8MThe Role of Inflammation and NGF Dysfunction in the Evolution of Alzheimer Disease Pathology in Down Syndrome-RevisionRF1AG056850 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BUSCIGLIO, JORGE A, CUELLO, A CLAUDIO · 2018 to 2020
$5.9MTau pathology in Down syndrome and Alzheimer'sRF1AG061566 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, MARGITTAI, MARTIN · 2019 to 2019
$3.4MRETINAL DEHYDROGENASESR01AG013566 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI NAPOLI, JOSEPH L · 1995 to 2009
$2.9MBiological Correlates of Alzheimer in Down Syndrome.R21AG056974 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER · 2017 to 2018
$414kNIAAA NIH HHS P50 AA011999NIA NIH HHS R01 AG013566NIA NIH HHS R21 AG056974NIA NIH HHS RF1 AG056850NIA NIH HHS RF1 AG061566
Abstract
Obesity and type 2 diabetes are associated with cognitive dysfunction. Because the hypothalamus is implicated in energy balance control and memory disorders, we hypothesized that specific neurons in this brain region are at the interface of metabolism and cognition. Acute obesogenic diet administration in mice impaired recognition memory due to defective production of the neurosteroid precursor pregnenolone in the hypothalamus. Genetic interference with pregnenolone synthesis by Star deletion in hypothalamic POMC, but not AgRP neurons, deteriorated recognition memory independently of metabolic disturbances. Our data suggest that pregnenolone's effects on cognitive function were mediated via an autocrine mechanism on POMC neurons, influencing hippocampal long-term potentiation. The relevance of central pregnenolone on cognition was also confirmed in metabolically unhealthy patients with obesity. Our data reveal an unsuspected role for POMC neuron-derived neurosteroids in cognition. These results provide the basis for a framework to investigate new facets of POMC neuron biology with implications for cognitive disorders.
Indexed as
Diabetes Mellitus, Type 2Metabolic DiseasesAnimalsHumansHypothalamusMiceMice, Inbred C57BLPregnenolonePro-OpiomelanocortinPregnenolonePro-Opiomelanocortincognitive functiondiabeteshypothalamusmitochondrianeurosteroidsobesityPOMC neuronspregnenolonerecognition memoryStard1
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