FICAM, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Cell Biology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
ALTEX. 2019;36(3):419-434. doi: 10.14573/altex.1811271. Epub 2019 Mar 15.
Besides being an energy storage, adipose tissue is an endocrine organ closely associated with vascular system. Human relevant in vitro models are needed to study adipose tissue and related diseases. Vasculature plays a central role in the development and inhibition of adipose tissue related diseases. Here, adipocyte culture was established from hASC (human adipose stromal cells), and a vascularized adipose tissue model was established from hASC and HUVEC (human umbilical cord vein endothelial cell) co-culture, utilizing the same differentiation procedure. Using these models together allowed analysis of the effect of vascularization on adipocytes. Adipocyte culture and Vascularized adipose tissue model were characterized on gene (adipocyte and vasculature-related), protein (von Willebrand factor, CollagenIV, CD140b and CD144, secretion of leptin, adiponectin and FABP4) and functional (triglyceride accumulation, glucose uptake and lipolysis) levels. Additionally, vascularized adipose tissue model was exposed to chemicals with known effects on adipogenesis and angiogenesis (rosiglitazone, chlorpyrifos, prochloraz, mancozeb, butylparaben, 15-deoxy-δ12,14-prostaglandin j2, bisphenol a, bis-(2-ethylhexyl) phthalate, tributyltin chloride) to compare their effects to the literature. The in vitro vascularized adipose tissue model showed presence of functional adipocytes and extensive vascular network. Adipocytes and the vasculature showed relevant gene and protein markers. Insulin induced glucose uptake, inhibited lipolysis and influenced vasculature-related genes. The results showed that vasculature led to faster insulin response in lipolysis inhibition and modulated responses to chemicals. This novel thoroughly characterized vascularized adipose tissue model is a promising new tool for studying adipose tissue as well as effect of chemicals on adipogenesis and angiogenesis in adipose tissue.
除了作为能量储存器外，脂肪组织还是一个与血管系统密切相关的内分泌器官。需要人类相关的体外模型来研究脂肪组织和相关疾病。血管在脂肪组织相关疾病的发展和抑制中起着核心作用。在这里，利用相同的分化程序，从 hASC（人脂肪基质细胞）中建立了脂肪细胞培养，从 hASC 和 HUVEC（人脐静脉内皮细胞）共培养中建立了血管化脂肪组织模型。使用这些模型一起可以分析血管化对脂肪细胞的影响。脂肪细胞培养和血管化脂肪组织模型在基因（脂肪细胞和血管相关）、蛋白质（血管性血友病因子、IV 型胶原、CD140b 和 CD144、瘦素、脂联素和 FABP4 的分泌）和功能（甘油三酯积累、葡萄糖摄取和脂肪分解）水平上进行了表征。此外，将血管化脂肪组织模型暴露于已知对脂肪生成和血管生成有影响的化学物质（罗格列酮、毒死蜱、丙环唑、代森锰锌、对羟基苯甲酸丁酯、15-脱氧-δ12,14-前列腺素 J2、双酚 A、邻苯二甲酸二（2-乙基己基）酯、三丁基锡氯化物）中，以比较它们与文献的影响。体外血管化脂肪组织模型显示存在功能脂肪细胞和广泛的血管网络。脂肪细胞和血管显示出相关的基因和蛋白质标志物。胰岛素诱导葡萄糖摄取，抑制脂肪分解，并影响血管相关基因。结果表明，血管化导致脂肪分解抑制中的胰岛素反应更快，并调节了对化学物质的反应。这种新型的经过充分表征的血管化脂肪组织模型是研究脂肪组织以及化学物质对脂肪生成和血管生成的影响的一种很有前途的新工具。
