학술논문
Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation.
Document Type
Academic Journal
Author
Milbank E; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; SOPAM, U1063, INSERM, University of Angers, SFR ICAT, Bat IRIS-IBS, Angers, France.; Dragano NRV; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; González-García I; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), German Center for Diabetes Research (DZD), Neuherberg, Germany.; Garcia MR; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Rivas-Limeres V; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Perdomo L; SOPAM, U1063, INSERM, University of Angers, SFR ICAT, Bat IRIS-IBS, Angers, France.; Hilairet G; SOPAM, U1063, INSERM, University of Angers, SFR ICAT, Bat IRIS-IBS, Angers, France.; Ruiz-Pino F; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain.; Mallegol P; SOPAM, U1063, INSERM, University of Angers, SFR ICAT, Bat IRIS-IBS, Angers, France.; Morgan DA; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.; Iglesias-Rey R; Clinical Neurosciences Research Laboratory, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; Contreras C; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Vergori L; SOPAM, U1063, INSERM, University of Angers, SFR ICAT, Bat IRIS-IBS, Angers, France.; Cuñarro J; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Porteiro B; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Gavaldà-Navarro A; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Institut de Biomedicina de la Universitat de Barcelona-Institut de Recerca Hospital Sant Joan de Déu, IBUB-IRSJD, Barcelona, Spain.; Oelkrug R; Institute for Endocrinology and Diabetes-Molecular Endocrinology, Center of Brain Behavior and Metabolism CBBM, University of Lübeck, Lübeck, Germany.; Vidal A; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; Roa J; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain.; Sobrino T; Clinical Neurosciences Research Laboratory, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; Villarroya F; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Institut de Biomedicina de la Universitat de Barcelona-Institut de Recerca Hospital Sant Joan de Déu, IBUB-IRSJD, Barcelona, Spain.; Diéguez C; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Nogueiras R; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; García-Cáceres C; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), German Center for Diabetes Research (DZD), Neuherberg, Germany.; Medizinische Klinik and Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany.; Tena-Sempere M; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain.; FiDiPro Program, Institute of Biomedicine, University of Turku, Turku, Finland.; Mittag J; Institute for Endocrinology and Diabetes-Molecular Endocrinology, Center of Brain Behavior and Metabolism CBBM, University of Lübeck, Lübeck, Germany.; Carmen Martínez M; SOPAM, U1063, INSERM, University of Angers, SFR ICAT, Bat IRIS-IBS, Angers, France.; Rahmouni K; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.; Andriantsitohaina R; SOPAM, U1063, INSERM, University of Angers, SFR ICAT, Bat IRIS-IBS, Angers, France. ramaroson.andriantsitohaina@inserm.fr.; López M; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain. m.lopez@usc.es.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain. m.lopez@usc.es.
Source
Publisher: Springer Nature Country of Publication: Germany NLM ID: 101736592 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2522-5812 (Electronic) Linking ISSN: 25225812 NLM ISO Abbreviation: Nat Metab Subsets: MEDLINE
Subject
Language
English
Abstract
Current pharmacological therapies for treating obesity are of limited efficacy. Genetic ablation or loss of function of AMP-activated protein kinase alpha 1 (AMPKα1) in steroidogenic factor 1 (SF1) neurons of the ventromedial nucleus of the hypothalamus (VMH) induces feeding-independent resistance to obesity due to sympathetic activation of brown adipose tissue (BAT) thermogenesis. Here, we show that body weight of obese mice can be reduced by intravenous injection of small extracellular vesicles (sEVs) delivering a plasmid encoding an AMPKα1 dominant negative mutant (AMPKα1-DN) targeted to VMH-SF1 neurons. The beneficial effect of SF1-AMPKα1-DN-loaded sEVs is feeding-independent and involves sympathetic nerve activation and increased UCP1-dependent thermogenesis in BAT. Our results underscore the potential of sEVs to specifically target AMPK in hypothalamic neurons and introduce a broader strategy to manipulate body weight and reduce obesity.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)