RT Journal Article
T1 Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation.
A1 Milbank, Edward
A1 Dragano, Nathalia R V
A1 González-García, Ismael
A1 Garcia, Marcos Rios
A1 Rivas-Limeres, Verónica
A1 Perdomo, Liliana
A1 Hilairet, Grégory
A1 Ruiz-Pino, Francisco
A1 Mallegol, Patricia
A1 Morgan, Donald A
A1 Iglesias-Rey, Ramón
A1 Contreras, Cristina
A1 Vergori, Luisa
A1 Cuñarro, Juan
A1 Porteiro, Begoña
A1 Gavaldà-Navarro, Aleix
A1 Oelkrug, Rebecca
A1 Vidal, Anxo
A1 Roa, Juan
A1 Sobrino, Tomás
A1 Villarroya, Francesc
A1 Diéguez, Carlos
A1 Nogueiras, Rubén
A1 García-Cáceres, Cristina
A1 Tena-Sempere, Manuel
A1 Mittag, Jens
A1 Carmen Martínez, M
A1 Rahmouni, Kamal
A1 Andriantsitohaina, Ramaroson
A1 López, Miguel
AB 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.
YR 2021
FD 2021-10-21
LK https://hdl.handle.net/10668/25515
UL https://hdl.handle.net/10668/25515
LA en
DS RISalud
RD Apr 5, 2025