| First Author | Wang J | Year | 2026 |
| Journal | Cell Metab | Volume | 38 |
| Issue | 1 | Pages | 82-99.e8 |
| PubMed ID | 41223857 | Mgi Jnum | J:386234 |
| Mgi Id | MGI:8272440 | Doi | 10.1016/j.cmet.2025.10.005 |
| Citation | Wang J, et al. (2025) Adipocyte-derived extracellular vesicles are key regulators of central leptin sensitivity and energy homeostasis. Cell Metab |
| abstractText | The exact mechanisms underlying leptin resistance, the central mechanism of obesity, remain elusive. Herein, we demonstrate that adipocyte-derived extracellular vesicles (Ad-EVs) serve as key regulatory factors of hypothalamic circuits governing food intake and body weight by modulating leptin responsiveness. Specifically, we identified a subset of microRNA (miRNA) within Ad-EVs that exerts leptin-sensitizing effects by inhibiting negative feedback regulators of leptin receptor signaling. Loss of these leptin-sensitizing miRNAs in Ad-EVs contributes to leptin resistance and subsequent weight gain in obesity. Of note, we developed engineered EVs modified with specific Ad-EV membrane proteins for targeted delivery of leptin-sensitizing miRNAs to the central nervous system, which reversed central leptin resistance and induced significant weight loss in obese mice. These findings highlight the critical role of Ad-EVs in central leptin sensitivity regulation, offering new insights into the role of the adipose tissue-brain axis in maintaining energy balance and potential pharmacological targets for obesity treatment. |
