Fang Jia
Henan Key Laboratory of Stem Cell Clinical Application and Key Technology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, Henan Province, China.
World J Stem Cells. 2025 Jun 26;17(6):104367. doi: 10.4252/wjsc.v17.i6.104367.
Hypertrophy obesity is closely associated with obesity-related metabolic diseases. The senescence of adipose-derived mesenchymal stem cells (ASCs) is believed to play a significant role in the development of hypertrophy obesity.
To investigate the relationship between ASC senescence, endoplasmic reticulum (ER) stress, and nuclear factor erythroid-derived 2 (NRF2) activity in a mouse model of hypertrophy obesity. Additionally, we explored the mechanism through which NRF2 affects ASC senescence mitofusin-2 (MFN2).
We observed the senescent phenotype and ER stress (ERS) in ASCs from hypertrophic obese mouse models, and determined NRF2 activity. Chromatin immunoprecipitation-quantitative polymerase chain reaction (qPCR) was used to analyze the transcriptional activity of NRF2 on . Additionally, co-immunoprecipitation experiments were conducted to investigate the interaction between MFN2 and binding immunoglobulin protein. The impact of NRF2 and MFN2 on the therapeutic effect of ASC transplantation against insulin resistance was explored through ASC transplantation.
The study found significant increases in senescence and ERS, accompanied by decreased NRF2 activity in ASCs from hypertrophic obese mouse models. Simultaneously, chromatin immunoprecipitation-qPCR analysis revealed a reduction in NRF2 transcriptional activity on . The downregulation of NRF2 activity and expression promoted senescence and ERS in ASCs, subsequently impacting the anti-insulin resistance effect of ASC transplantation. Furthermore, there exists a direct or indirect binding between MFN2 and binding immunoglobulin protein.
The research outcomes suggest that NRF2 may regulate ERS and senescence in subcutaneous ASCs of hypertrophic obese mice by modulating . These discoveries offer new insights into understanding metabolic diseases associated with hypertrophic obesity and potentially provide a foundation for intervention strategies.
肥大性肥胖与肥胖相关的代谢性疾病密切相关。脂肪来源的间充质干细胞（ASC）的衰老被认为在肥大性肥胖的发展中起重要作用。
在肥大性肥胖小鼠模型中研究ASC衰老、内质网（ER）应激和核因子红细胞衍生2（NRF2）活性之间的关系。此外，我们探讨了NRF2通过丝裂原活化蛋白激酶2（MFN2）影响ASC衰老的机制。
我们观察了肥大性肥胖小鼠模型中ASC的衰老表型和ER应激（ERS），并测定了NRF2活性。采用染色质免疫沉淀-定量聚合酶链反应（qPCR）分析NRF2对……的转录活性。此外，进行了免疫共沉淀实验以研究MFN2与结合免疫球蛋白蛋白之间的相互作用。通过ASC移植探讨NRF2和MFN2对ASC移植抗胰岛素抵抗治疗效果的影响。
研究发现肥大性肥胖小鼠模型的ASC中衰老和ERS显著增加，同时NRF2活性降低。同时，染色质免疫沉淀-qPCR分析显示NRF2对……的转录活性降低。NRF2活性和……表达的下调促进了ASC的衰老和ERS，随后影响了ASC移植的抗胰岛素抵抗作用。此外，MFN2与结合免疫球蛋白蛋白之间存在直接或间接结合。
研究结果表明，NRF2可能通过调节……来调节肥大性肥胖小鼠皮下ASC中的ERS和衰老。这些发现为理解与肥大性肥胖相关的代谢性疾病提供了新的见解，并可能为干预策略提供基础。
