Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity

Authors

Qing Zhou
Jia Gao
Guorao Wu
Chenwei Wang
Yan Yang
Teng Huang
Yi Wang
Tiantian Yue
Zhichao Gao
Hao Xie
Fei Xiong
Ke Xiang
Tuying Yong
Wanguang Zhang
Tongtong Zhang
Wen Kong
Cai Chen
Shu Zhang
Qilin Yu
Xuemei Fan
Shiwei Liu
Yanjun Liu
Cong-Yi Wang

Language

English

Publication Date

3-20-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-57444-y

PMID

40113754

PMCID

PMC11926339

PubMedCentral® Posted Date

5-20-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs from young APCs effectively inhibit M1 macrophage polarization. Accordingly, targeted liposomes are designed to deliver miR-145-5p mimics to ATMs, which effectively prevent the obesity in middle-aged mice. Collectively, our findings highlight the role of APC-derived EVs in midlife obesity and propose miR-145-5pas a promising therapeutic target for clinical applications.

Keywords

Extracellular Vesicles, Animals, Obesity, MicroRNAs, Macrophages, Mice, Humans, Middle Aged, Adipose Tissue, White, Stem Cells, Male, Female, Mice, Inbred C57BL, Signal Transduction, NF-kappa B, Adipose Tissue, Obesity, Obesity, Drug delivery

Published Open-Access

yes

Recommended Citation

Zhou, Qing; Gao, Jia; Wu, Guorao; et al., "Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity" (2025). Children’s Nutrition Research Center Staff Publications. 310.
https://digitalcommons.library.tmc.edu/staff_pub/310