香港大学徐爱民团队的一项最新研究显示，肠道微生物群-脂肪相互作用调节可溶性IL-6受体，影响血糖控制和胰岛素敏感性的运动反应性。相关论文于2025年11月18日发表在《细胞—代谢》杂志上。

在此，课题组人员确定脂肪细胞衍生的可溶性白细胞介素-6受体（sIL-6R）是决定运动在改善代谢健康方面功效的关键运动因子。在接受12周运动干预的肥胖个体中，循环sIL-6R水平在运动反应者（Rs）和无反应者（NRs）之间表现出二分类变化，与运动介导的胰岛素敏感性和血糖控制的改变密切相关。机制上，NR中升高的肠道微生物介导的亮氨酸通过雷帕霉素(mTOR)-缺氧诱导因子1α (HIF1α)的哺乳动物靶点，作用于白色脂肪细胞，促进崩解素和金属蛋白酶17 （ADAM17）介导的sIL-6R的产生，进而通过白细胞介素(IL)-6反式信号诱导的脂肪炎症损害运动的代谢益处。脂肪细胞选择性消融ADAM17可阻止NR粪便微生物群移植对sIL-6R升高的影响，从而恢复运动型肠道微生物群对抗肥胖小鼠葡萄糖耐受不良和胰岛素抵抗的功效。因此，针对脂肪细胞衍生的sIL-6R的治疗干预代表了在个性化糖尿病预防中最大化运动功效的有希望的策略。

据了解，运动是预防和控制糖尿病的有效干预手段，但人与人之间对运动反应的高度变异性阻碍了运动的广泛实施。

附：英文原文

Title: Gut microbiome-adipose crosstalk modulates soluble IL-6 receptor influencing exercise responsiveness in glycemic control and insulin sensitivity

Author: Yao Wang, Jiaming Wu, Jianyu Yao, Jiarui Chen, Kenneth K.Y. Cheng, Melody Yuen-man Ho, Chi Ho Lee, Karen Siu-Ling Lam, Michael Andrew Tse, Gianni Panagiotou, Aimin Xu

Issue&Volume: 2025-11-18

Abstract: Exercise is an effective intervention for the prevention and management of diabetes, but the high interpersonal variability in response to exercise impedes its widespread implementation. Herein, we identify adipocyte-derived soluble interleukin-6 receptor (sIL-6R) as a key exerkine determining exercise efficacy in improving metabolic health. In individuals with obesity who underwent a 12-week exercise intervention, circulating sIL-6R level exhibits dichotomous changes between exercise responders (Rs) and non-responders (NRs), in close association with exercise-mediated alterations in insulin sensitivity and glycemic control. Mechanistically, elevated gut microbiome-mediated leucine in NR acts on white adipocytes to promote disintegrin and metalloproteinase 17 (ADAM17)-mediated sIL-6R production via the mammalian target of rapamycin (mTOR)-hypoxia-inducible factor 1α (HIF1α) pathway, which in turn impairs the metabolic benefits of exercise through interleukin (IL)-6 trans-signaling-induced adipose inflammation. Adipocyte-selective ablation of ADAM17 prevents the effects of fecal microbiota transplantation from NR on elevation of sIL-6R, thereby restoring the efficacy of exercise-shaped gut microbiome in counteracting glucose intolerance and insulin resistance in obese mice. Thus, therapeutic interventions targeting adipocyte-derived sIL-6R represent a promising strategy for maximizing exercise efficacy in personalized diabetes prevention.

DOI: 10.1016/j.cmet.2025.10.013

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00473-5