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Endothelial cell crosstalk improves browning but hinders white adipocyte maturation in 3D engineered adipose tissue.
Integrative Biology ( IF 1.5 ) Pub Date : 2020-04-20 , DOI: 10.1093/intbio/zyaa006
Jennifer H Hammel 1 , Evangelia Bellas 1
Affiliation  

Central to the development of adipose tissue (AT) engineered models is the supporting vasculature. It is a key part of AT function and long-term maintenance, but the crosstalk between adipocytes and endothelial cells is not well understood. Here, we directly co-culture the two cell types at varying ratios in a 3D Type I collagen gel. Constructs were evaluated for adipocyte maturation and function and vascular network organization. Further, these constructs were treated with forskolin, a beta-adrenergic agonist, to stimulate lipolysis and browning. Adipocytes in co-cultures were found to be less mature than an adipocyte-only control, shown by smaller lipid droplets and downregulation of key adipocyte-related genes. The most extensive vascular network formation was found in the 1:1 co-culture, supported by vascular endothelial growth factor (VEGF) upregulation. After forskolin treatment, the presence of endothelial cells was shown to upregulate PPAR coactivator 1 alpha (PGC-1α) and leptin, but not uncoupling protein 1 (UCP1), suggesting a specific crosstalk that enhances early stages of browning.

中文翻译:

内皮细胞串扰可改善褐变,但会阻碍3D工程脂肪组织中白色脂肪细胞的成熟。

支持脂肪组织是脂肪组织(AT)工程模型开发的核心。它是AT功能和长期维持的关键部分,但脂肪细胞与内皮细胞之间的串扰尚不十分清楚。在这里,我们在3D I型胶原蛋白凝胶中以不同的比例直接共培养两种细胞类型。评价构建体的脂肪细胞成熟和功能以及血管网络的组织。此外,将这些构建体用β-肾上腺素激动剂福斯高林处理,以刺激脂解和褐变。发现共培养中的脂肪细胞比仅脂肪细胞的对照成熟度低,这是由较小的脂滴和关键的与脂肪细胞相关的基因下调所显示的。在1:1的共培养物中发现了最广泛的血管网络形成,由血管内皮生长因子(VEGF)上调支持。经福司高林处理后,内皮细胞的存在可上调PPAR共激活因子1α(PGC-1α)和瘦素,但不解偶联蛋白1(UCP1),提示特定的串扰可增强褐变的早期阶段。
更新日期:2020-04-20
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