近日，北京大学教授肖瑞平及其团队报道了MIF-ACKR3通过损害癌症恶病质中的脂肪生成导致不可逆的脂肪减少。这一研究成果发表在2025年2月27日出版的国际学术期刊《细胞—代谢》上。

研究小组发现肿瘤分泌的巨噬细胞迁移抑制因子（MIF）是导致脂肪干细胞和祖细胞（ASPCs）向促炎和促纤维化方向分化的主要驱动因素，在癌症恶病质中导致脂肪生成能力降低。相反，运动后循环MIF适度减少。在机制上，非典型趋化因子受体3 （ACKR3）在ASPCs中作为主要的MIF受体介导其病理作用。通过肿瘤细胞中的基因消融或药物阻断抑制MIF，以及ASPCs特异性ACKR3缺陷，可显著缓解肿瘤诱导的恶病质。这些发现揭示了MIF-ACKR3信号作为肿瘤和恶病质表现之间的关键联系，为癌症恶病质提供了一个有希望的治疗靶点。

据悉，运动和癌症都能抑制脂肪组织的萎缩。然而，只有癌症相关的体重减轻，即恶病质，以严重的脂肪炎症和纤维化为特征。

附：英文原文

Title: MIF-ACKR3 causes irreversible fat loss by impairing adipogenesis in cancer cachexia

Author: Qionghua Cui, Shijin Li, Xidan Liu, Jie Liu, Wenxin Chen, Ye Sheng, Peng Xie, Li Jin, Fanxin Zeng, Fengxiang Lv, Xinli Hu, Rui-Ping Xiao

Issue&Volume: 2025-02-27

Abstract: Both exercise and cancer can cause adipose tissue shrinkage. However, only cancer-associated weight loss, namely cachexia, is characterized by profound adipose inflammation and fibrosis. Here, we identified tumor-secreted macrophage migration inhibitory factor (MIF) as a major driver that skews the differentiation of adipose stem and progenitor cells (ASPCs) toward a pro-inflammatory and pro-fibrogenic direction, with reduced adipogenic capacity in cancer cachexia. By contrast, circulating MIF is moderately reduced after exercise. Mechanistically, atypical chemokine receptor 3 (ACKR3) in ASPCs serves as the predominant MIF receptor mediating its pathological effects. Inhibition of MIF by gene ablation in tumor cells or pharmacological blockade, as well as ASPC-specific Ackr3 deficiency, markedly alleviates tumor-induced cachexia. These findings unveil MIF-ACKR3 signaling as a critical link between tumors and cachectic manifestations, providing a promising therapeutic target for cancer cachexia.

DOI: 10.1016/j.cmet.2025.01.018

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00018-X