| Literature DB >> 34675439 |
Edward Milbank1,2,3, Nathalia R V Dragano1,2, Ismael González-García1,2,4, Marcos Rios Garcia1,2, Verónica Rivas-Limeres1,2, Liliana Perdomo3, Grégory Hilairet3, Francisco Ruiz-Pino2,5, Patricia Mallegol3, Donald A Morgan6, Ramón Iglesias-Rey7, Cristina Contreras1,2, Luisa Vergori3, Juan Cuñarro1,2, Begoña Porteiro1,2, Aleix Gavaldà-Navarro2,8, Rebecca Oelkrug9, Anxo Vidal1, Juan Roa2,5, Tomás Sobrino7, Francesc Villarroya2,8, Carlos Diéguez1,2, Rubén Nogueiras1,2, Cristina García-Cáceres4,10, Manuel Tena-Sempere2,5,11, Jens Mittag9, M Carmen Martínez3, Kamal Rahmouni6, Ramaroson Andriantsitohaina12, Miguel López13,14.
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.Entities:
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Year: 2021 PMID： 34675439 DOI： 10.1038/s42255-021-00467-8
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812