Pérez Laura M, de Lucas Beatriz, Gálvez Beatriz G
Health and Biomedical Sciences Faculty, European University, Madrid, Spain.
J Cell Physiol. 2021 Jan;236(1):132-145. doi: 10.1002/jcp.29829. Epub 2020 May 29.
Pericardial adipose tissue (PAT), a visceral fat depot enveloping the heart, is an active endocrine organ and a source of free fatty acids and inflammatory cytokines. As in other fat adult tissues, PAT contains a population of adipose stem cells; however, whether these cells and/or their environment play a role in physiopathology is unknown. We analyzed several stem cell-related properties of pericardial adipose stem cells (PSCs) isolated from obese and ex-obese mice. We also performed RNA-sequencing to profile the transcriptional landscape of PSCs isolated from the different diet regimens. Finally, we tested whether these alterations impacted on the properties of cardiac mesoangioblasts isolated from the same mice. We found functional differences between PSCs depending on their source: specifically, PSCs from obese PSC (oPSC) and ex-obese PSC (dPSC) mice showed alterations in apoptosis and migratory capacity when compared with lean, control PSCs, with increased apoptosis in oPSCs and blunted migratory capacity in oPSCs and dPSCs. This was accompanied by different gene expression profiles across the cell types, where we identified some genes altered in obese conditions, such as BMP endothelial cell precursor-derived regulator (BMPER), an important regulator of BMP-related signaling pathways for endothelial cell function. The importance of BMPER in PSCs was confirmed by loss- and gain-of-function studies. Finally, we found an altered production of BMPER and some important chemokines in cardiac mesoangioblasts in obese conditions. Our findings point to BMPER as a potential new regulator of PSC function and suggest that its dysregulation could be associated with obesity and may impact on cardiac cells.
心包脂肪组织（PAT）是包裹心脏的内脏脂肪库，是一个活跃的内分泌器官，也是游离脂肪酸和炎性细胞因子的来源。与其他成年脂肪组织一样，PAT含有一群脂肪干细胞；然而，这些细胞和/或其环境是否在病理生理学中发挥作用尚不清楚。我们分析了从肥胖和肥胖后小鼠中分离的心包脂肪干细胞（PSC）的几种与干细胞相关的特性。我们还进行了RNA测序，以描绘从不同饮食方案中分离出的PSC的转录图谱。最后，我们测试了这些改变是否会影响从同一小鼠中分离出的心脏间充质血管祖细胞的特性。我们发现PSC之间存在功能差异，这取决于它们的来源：具体而言，与瘦的对照PSC相比，来自肥胖PSC（oPSC）和肥胖后PSC（dPSC）小鼠的PSC在凋亡和迁移能力方面表现出改变，oPSC中的凋亡增加，oPSC和dPSC中的迁移能力减弱。这伴随着不同细胞类型之间不同的基因表达谱，我们在其中鉴定出一些在肥胖条件下改变的基因，例如BMP内皮细胞前体衍生调节剂（BMPER），它是内皮细胞功能的BMP相关信号通路的重要调节剂。功能丧失和功能获得研究证实了BMPER在PSC中的重要性。最后，我们发现在肥胖条件下心脏间充质血管祖细胞中BMPER和一些重要趋化因子的产生发生了改变。我们的研究结果表明BMPER是PSC功能的潜在新调节剂，并表明其失调可能与肥胖有关，并且可能影响心脏细胞。
