Succinate diminishes biological activity and mitochondrial function of human adipose-derived stem cells

Alterations in succinate levels have been associated with various metabolic and inflammatory diseases. However, little is currently known about whether adipose-derived stem cells (ADSCs) undergo changes when exposed to succinate. Here, we investigate the biological properties, mitochondrial function and immunophenotype of ADSCs treated with succinate. We observed that reduced biological activity of ADSCs following by succinate stimulated. Of note, succinate treated-ADSCs exhibit mitochondrial dysfunctions, including increased mitochondrial fragments, decreased mitochondrial mass, increased ROS production, reduced Oxidative phosphorylation (OXPHOS). Furthermore, transcriptome analysis revealed that the downregulation of genes involved in cell proliferation, OXPHOS and metabolism, whereas the signaling pathways related to cancer, apoptosis, inflammation were upregulated upon succinate treatment. The findings indicate that ADSCs exposed to succinate exhibit signs of mitochondrial dysfunction, inflammation, and a significant decrease in biological activity. Comparative gene expression profiling analysis of RNA-seq data for Adipose stem cells treated with DMS and DMM versus control.

琥珀酸水平的异常改变与多种代谢性及炎症性疾病密切相关。然而，目前学界对于脂肪来源干细胞（adipose-derived stem cells, ADSCs）暴露于琥珀酸时是否会发生变化尚不清楚。本研究针对琥珀酸处理后的ADSCs，探究其生物学特性、线粒体功能及免疫表型。我们观察到，琥珀酸刺激后ADSCs的生物学活性显著降低。值得注意的是，经琥珀酸处理的ADSCs出现线粒体功能异常，具体表现为线粒体片段化程度升高、线粒体质量下降、活性氧（reactive oxygen species, ROS）生成增加以及氧化磷酸化（Oxidative phosphorylation, OXPHOS）水平降低。此外，转录组分析结果显示，参与细胞增殖、氧化磷酸化及代谢过程的基因表达显著下调，而与癌症、细胞凋亡、炎症相关的信号通路在琥珀酸处理后出现上调。本研究结果表明，暴露于琥珀酸的ADSCs会出现线粒体功能异常、炎症反应，且生物学活性显著下降。本研究针对经DMS、DMM处理与对照组的脂肪干细胞的RNA测序数据开展比较基因表达谱分析。