| First Author | Milbank E | Year | 2023 |
| Journal | Metabolism | Volume | 139 |
| Pages | 155350 | PubMed ID | 36423694 |
| Mgi Jnum | J:332416 | Mgi Id | MGI:7424583 |
| Doi | 10.1016/j.metabol.2022.155350 | Citation | Milbank E, et al. (2023) Small extracellular vesicle targeting of hypothalamic AMPKalpha1 promotes weight loss in leptin receptor deficient mice. Metabolism 139:155350 |
| abstractText | 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 (AMPKalpha1-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-AMPKalpha1-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. |
