脂肪细胞衍生的细胞外囊泡是中枢瘦素敏感性和能量稳态的关键调节因子，这一成果由南京大学毕艳课题组经过不懈努力而取得。该研究于2025年11月11日发表于国际一流学术期刊《细胞—代谢》杂志上。

在此，课题组研究人员证明脂肪细胞衍生的细胞外囊泡（Ad-EVs）通过调节瘦素反应作为下丘脑回路控制食物摄入和体重的关键调节因子。具体来说，小组在Ad-EVs中发现了一个microRNA （miRNA）亚群，它通过抑制瘦素受体信号的负反馈调节来发挥瘦素增敏作用。Ad-EVs中这些瘦素敏感miRNA的缺失有助于瘦素抵抗和随后的肥胖体重增加。

值得注意的是，课题组开发了用特异性Ad-EV膜蛋白修饰的工程化EV，用于将瘦素敏感miRNA靶向递送到中枢神经系统，从而逆转了肥胖小鼠的中枢瘦素抵抗并诱导了显著的体重减轻。这些发现强调了Ad-EV在中枢瘦素敏感性调节中的关键作用，为脂肪组织-脑轴在维持能量平衡中的作用和肥胖治疗的潜在药理靶点提供了新的见解。

研究人员表示，瘦素抵抗的确切机制，肥胖的核心机制，仍然是未知的。

附：英文原文

Title: Adipocyte-derived extracellular vesicles are key regulators of central leptin sensitivity and energy homeostasis

Author: Jin Wang, Xuhong Zhang, Ye Zhu, Haixiang Sun, Xuetao Chen, Zhicong Zhao, Nina Zhang, Chenyu Zhang, Liang Li, Yan Bi

Issue&Volume: 2025-11-11

Abstract: 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.

DOI: 10.1016/j.cmet.2025.10.005

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00439-5