Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation.

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dc.contributor.authorMilbank, Edward
dc.contributor.authorDragano, Nathalia R V
dc.contributor.authorGonzález-García, Ismael
dc.contributor.authorGarcia, Marcos Rios
dc.contributor.authorRivas-Limeres, Verónica
dc.contributor.authorPerdomo, Liliana
dc.contributor.authorHilairet, Grégory
dc.contributor.authorRuiz-Pino, Francisco
dc.contributor.authorMallegol, Patricia
dc.contributor.authorMorgan, Donald A
dc.contributor.authorIglesias-Rey, Ramón
dc.contributor.authorContreras, Cristina
dc.contributor.authorVergori, Luisa
dc.contributor.authorCuñarro, Juan
dc.contributor.authorPorteiro, Begoña
dc.contributor.authorGavaldà-Navarro, Aleix
dc.contributor.authorOelkrug, Rebecca
dc.contributor.authorVidal, Anxo
dc.contributor.authorRoa, Juan
dc.contributor.authorSobrino, Tomás
dc.contributor.authorVillarroya, Francesc
dc.contributor.authorDiéguez, Carlos
dc.contributor.authorNogueiras, Rubén
dc.contributor.authorGarcía-Cáceres, Cristina
dc.contributor.authorTena-Sempere, Manuel
dc.contributor.authorMittag, Jens
dc.contributor.authorCarmen Martínez, M
dc.contributor.authorRahmouni, Kamal
dc.contributor.authorAndriantsitohaina, Ramaroson
dc.contributor.authorLópez, Miguel
dc.date.accessioned2025-01-07T13:27:05Z
dc.date.available2025-01-07T13:27:05Z
dc.date.issued2021-10-21
dc.description.abstractCurrent 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.
dc.identifier.doi10.1038/s42255-021-00467-8
dc.identifier.essn2522-5812
dc.identifier.pmid34675439
dc.identifier.pubmedURLhttps://pmc.ncbi.nlm.nih.gov/articles/8904083/pdf
dc.identifier.urihttps://hdl.handle.net/10668/25515
dc.issue.number10
dc.journal.titleNature metabolism
dc.journal.titleabbreviationNat Metab
dc.language.isoen
dc.organizationSAS - Hospital Universitario Reina Sofía
dc.organizationInstituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)
dc.page.number1415-1431
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.pubmedtypeResearch Support, U.S. Gov't, Non-P.H.S.
dc.subject.meshAMP-Activated Protein Kinases
dc.subject.meshAdipose Tissue, Brown
dc.subject.meshAnimals
dc.subject.meshEnergy Metabolism
dc.subject.meshExtracellular Vesicles
dc.subject.meshHypothalamus
dc.subject.meshMice
dc.subject.meshObesity
dc.subject.meshThermogenesis
dc.subject.meshWeight Loss
dc.titleSmall extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation.
dc.typeresearch article
dc.volume.number3

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