期刊
METABOLISM-CLINICAL AND EXPERIMENTAL
卷 139, 期 -, 页码 -出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2022.155350
关键词
Leptin receptor deficiency; db; db mice; Hypothalamus; AMPK; sEVs
The study found that using a specific type of extracellular vesicles loaded with a defective AMPK alpha 1 gene can alleviate symptoms such as obesity and metabolic disorders in mice.
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 (AMPK alpha 1-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-AMPK alpha 1-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.
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