| Autor: |
Edward Milbank, Nathalia Dragano, Xavi Vidal-Gómez, Verónica Rivas-Limeres, Pablo Garrido-Gil, Mireille Wertheimer, Sylvain Recoquillon, María P. Pata, José Luis Labandeira-Garcia, Carlos Diéguez, Rubén Nogueiras, M. Carmen Martínez, Ramaroson Andriantsitohaina, Miguel López |
| Přispěvatelé: |
Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Fisioloxía |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Metabolism: clinical and experimental. 139 |
| ISSN: |
1532-8600 |
| Popis: |
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 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) SI |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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