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单细胞转录组学揭示了在早期肥胖相关的慢性病期间在淋巴细胞中由阿波利波蛋白A4介导的代谢-免疫重编程

Yang Wei^1,2, Ting Zhang², Yingying Jin³

¹Department of Pathology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

Acta biochimica et biophysica Sinica

|September 26, 2025

概括

脂蛋白A4 (Apoa4) 缺乏会使肥胖相关的脏炎症和免疫细胞功能障碍恶化. 在慢性病 (CKD) 的早期阶段,Apoa4对于维持免疫平衡至关重要.

科学领域:

免疫学免疫学免疫学
代谢疾病代谢疾病
腎臟病學 (nephrology) 是一種醫學專業.

背景情况:

肥胖引起的代谢炎症驱动慢性病 (CKD).
免疫失调,特别是淋巴细胞,有助于早期CKD病理.
阿波利波蛋白A4 (Apoa4) 在肥胖相关的CKD期间免疫细胞代谢和功能中的作用尚不清楚.

研究的目的:

研究Apoa4在调节高脂肪饮食诱导肥胖 (DIO) 小鼠免疫细胞代谢和功能中的作用.
阐明Apoa4删除对脏免疫代谢格局和早期CKD中淋巴细胞功能的影响.

主要方法:

已建立的DIO模型使用野生类型和Apoa4-Knockout (KO) 鼠标.
利用单细胞RNA测序来分析脏免疫细胞群和基因表达.
采用流细胞计,免疫光染色和qPCR进行验证.
进行了CellChat分析,以预测信号通路中断.

主要成果:

Apoa4 KO小鼠显示胰岛素耐药性加剧和脏脂质积累.
Apoa4的删除重塑了脏的免疫代谢格局,损害了T,NK和B细胞的功能.
代谢失调,氧化应激和关键效应基因 (例如,Ifng,Il1b) 的下调在KO小鼠中加剧.
观察到转录因子网络和信号通路 (例如,IFN-II,IL-1,FASLG,ENHO,ANGPTL) 的乱.

结论:

Apoa4在维持淋巴细胞代谢和免疫平衡中发挥着至关重要的作用.
在早期与肥胖相关的CKD中,Apoa4缺乏会加剧免疫功能障碍和代谢障碍.
向Apoa4可能为管理早期肥胖相关脏疾病提供治疗策略.

关键词:

在 Apoa4a4 慢性脏疾病慢性脏疾病免疫系统是免疫系统的.代谢代谢代谢代谢肥胖肥胖肥胖肥胖肥胖肥胖肥胖肥胖一个单细胞RNA测序.

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