小柯机器人

北京大学Li Qiang和Liheng Wang小组合作在研究中取得进展。他们的研究表明IgG是促使脂肪组织纤维化和代谢减慢的衰老因子。这一研究成果发表在2024年2月19日出版的国际学术期刊《细胞-代谢》上。

研究人员发现IgG在衰老过程中会发生积累，尤其是在白色脂肪组织（WAT）中，这会损害脂肪组织的功能和代谢健康。热量限制（CR）会减少IgG在白脂肪组织中的积累，而补充IgG则会抵消CR带来的代谢益处。IgG通过Ras信号激活巨噬细胞，进而利用TGF-β/SMAD途径诱导脂肪组织纤维化。

与此一致，除非暴露于IgG，否则缺乏B细胞的小鼠不会出现与衰老相关的WAT纤维化、炎症和胰岛素抵抗。条件性敲除巨噬细胞中的IgG循环受体-新生儿Fc受体（FcRn）-可防止衰老过程中IgG的累积，从而延长健康和寿命。

此外，通过反义寡核苷酸靶向FcRn能恢复老龄小鼠体内WAT的完整性和代谢健康。这些发现表明IgG是造成衰老的隐性罪魁祸首，并提出了一种恢复代谢健康的新策略。

据介绍，衰老具有明显的新陈代谢减弱；然而，衰老的诱导因素仍有待阐明。

附：英文原文

Title: IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline

Author: Lexiang Yu, Qianfen Wan, Qiongming Liu, Yong Fan, Qiuzhong Zhou, Alicja A. Skowronski, Summer Wang, Zhengping Shao, Chen-Yu Liao, Lei Ding, Brian K. Kennedy, Shan Zha, Jianwen Que, Charles A. LeDuc, Lei Sun, Liheng Wang, Li Qiang

Issue&Volume: 2024-02-19

Abstract: Aging is underpinned by pronounced metabolic decline; however, the drivers remainobscure. Here, we report that IgG accumulates during aging, particularly in whiteadipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloricrestriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteractsCR’s metabolic benefits. IgG activates macrophages via Ras signaling and consequentlyinduces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B cell nullmice are protected from aging-associated WAT fibrosis, inflammation, and insulin resistance,unless exposed to IgG. Conditional ablation of the IgG recycling receptor, neonatalFc receptor (FcRn), in macrophages prevents IgG accumulation in aging, resulting inprolonged healthspan and lifespan. Further, targeting FcRn by antisense oligonucleotiderestores WAT integrity and metabolic health in aged mice. These findings pinpointIgG as a hidden culprit in aging and enlighten a novel strategy to rejuvenate metabolic health.

DOI: 10.1016/j.cmet.2024.01.015

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00015-9

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