RT Journal Article
T1 Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice
A1 Milbank, Edward
A1 Dragano, Nathalia
A1 Vidal Gómez, Xavi
A1 Rivas Limeres, Verónica
A1 Garrido Gil, Pablo
A1 Wertheimer, Mireille
A1 Recoquillon, Sylvain
A1 Pata, María P.
A1 Labandeira García, José Luis
A1 Diéguez González, Carlos
A1 Nogueiras Pozo, Rubén
A1 Martínez, Marie Carmen
A1 Andriantsitohaina, Ramaroson
A1 López Pérez, Miguel A.
K1 Leptin receptor deficiency
K1 db/db mice
K1 Hypothalamus
K1 AMPK
K1 sEVs
AB 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
PB Elsevier
SN 0026-0495
YR 2023
FD 2023
LK http://hdl.handle.net/10347/30307
UL http://hdl.handle.net/10347/30307
LA eng
NO Metabolism 139 (2023) 155350. https://doi.org/10.1016/j.metabol.2022.155350
NO Ministerio de Ciencia y Universidades co-funded by the FEDER Program of EU (CD: BFU2017-87721; RN: RTI2018-099413-B-I00 and RED2018-102379-T; ML: RTI2018-101840-B-I00, PID2021-128145NB-I00 and PDC2022-133958-I00). “la Caixa” Foundation (ID100010434), under the agreement LCF/PR/HR19/52160022 (ML); EuroNanoMed III (RA & ML: EURONANOMED2019-050-ENAMEP); European Research Council (RN: ERC Synergy Grant-2019-WATCH-810331)
DS Minerva
RD 24 abr 2026