Transmissible Endoplasmic Reticulum Stress Mediated by Extracellular Vesicles from Adipocyte Promoting the Senescence of Adipose-Derived Mesenchymal Stem Cells in Hypertrophic Obesity

Author:

Fang Jia1ORCID,Li Li1,Cao Xingguo1,Yue Han2,Fu Wanying3,Chen Yi1,Xu Zhiwei1,Zhao Qiongrui1,Zhao Jingge1,Wang Yuebo1,Liang Wulong4ORCID

Affiliation:

1. Clinical Research Service Center, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan 450000, China

2. Stem Cell Research Center, Henan Key Laboratory of Stem Cell Differentiation and Modification, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital; Henan University People’s Hospital, Zhengzhou, Henan 450000, China

3. School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, China

4. Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China

Abstract

Hypertrophic obesity, characterized by an excessive expansion of subcutaneous adipocytes, causes chronic inflammation and insulin resistance. It is the primary feature of obesity in middle-aged and elderly individuals. In the adipose microenvironment, a high level of endoplasmic reticulum (ER) stress and changes in the extracellular vesicle (EV) composition of adipocytes may cause the senescence and restrained differentiation of progenitor cells of adipose, including adipose-derived mesenchymal stem cells (ASCs). In this study, a hypertrophic obesity mouse model was established, and the effects of adipocytes on the ER stress and senescence of ASCs were observed in a coculture of control ASCs and hypertrophic obesity mouse adipocytes or their derived EVs. The adipocytes of hypertrophic obesity mice were treated with GW4869 or an iron chelation agent to observe the effects of EVs secreted by adipocytes and their iron contents on the ER stress and senescence of ASCs. Results showed higher ER stress level and senescence phenotypes in the ASCs from the hypertrophic obesity mice than in those from the control mice. The ER stress, senescence phenotypes, and ferritin level of ASCs can be aggravated by the coculture of ASCs with adipocytes or EVs released by them from the hypertrophic obesity mice. GW4869 or iron chelator treatment improved the ER stress and senescence of the ASCs cocultured with EVs released by the adipocytes of the hypertrophic obesity mice. Our findings suggest that EV-mediated transmissible ER stress is responsible for the senescence of ASCs in hypertrophic obesity mice.

Funder

Scientific Startup Foundation for Doctors of Henan Provincial People’s Hospital

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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