Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice
Por favor, use este identificador para citas ou ligazóns a este ítem:
http://hdl.handle.net/10347/30307
Ficheiros no ítem
Metadatos do ítem
Título: | Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice |
Autor/a: | Milbank, Edward Dragano, Nathalia Vidal Gómez, Xavi Rivas Limeres, Verónica Garrido Gil, Pablo Wertheimer, Mireille Recoquillon, Sylvain Pata, María P. Labandeira García, José Luis Diéguez González, Carlos Nogueiras Pozo, Rubén Martínez, Marie Carmen Andriantsitohaina, Ramaroson López Pérez, Miguel Antonio |
Centro/Departamento: | Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas Universidade de Santiago de Compostela. Departamento de Fisioloxía |
Palabras chave: | Leptin receptor deficiency | db/db mice | Hypothalamus | AMPK | sEVs | |
Data: | 2023 |
Editor: | Elsevier |
Cita bibliográfica: | Metabolism 139 (2023) 155350. https://doi.org/10.1016/j.metabol.2022.155350 |
Resumo: | Background and aims: Leptin receptor (LEPR) deficiency promotes severe obesity and metabolic disorders. However, the current therapeutic options against this syndrome are scarce. Methods: db/db mice and their wildtypes were systemically treated with neuronal-targeted small extracellular vesicles (sEVs) harboring a plasmid encoding a dominant negative mutant of AMP-activated protein kinase alpha 1 (AMPKα1-DN) driven by steroidogenic factor 1 (SF1) promoter; this approach allowed to modulate AMPK activity, specifically in SF1 cells of the ventromedial nucleus of the hypothalamus (VMH). Animals were metabolically phenotyped. Results: db/db mice intravenously injected with SF1-AMPKα1-DN loaded sEVs showed a marked feeding-independent weight loss and decreased adiposity, associated with increased sympathetic tone, brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT).Conclusion: Overall, this evidence indicates that specific modulation of hypothalamic AMPK using a sEV-based technology may be a suitable strategy against genetic forms of obesity, such as LEPR deficiency |
Versión do editor: | https://doi.org/10.1016/j.metabol.2022.155350 |
URI: | http://hdl.handle.net/10347/30307 |
DOI: | 10.1016/j.metabol.2022.155350 |
ISSN: | 0026-0495 |
Dereitos: | © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Atribución 4.0 Internacional |
Coleccións
-
- CIMUS-Artigos [249]
- FIS-Artigos [114]
O ítem ten asociados os seguintes ficheiros de licenza: