Adipose models have been applied to mechanistic studies of metabolic diseases (such as diabetes) and the subsequent discovery of new therapeutics. However, typical models are either insufficiently complex (2D cell cultures) or expensive and labor intensive (mice/in vivo). To bridge the gap between these models and in order to better inform pre-clinical studies we have developed a drug-responsive 3D model of white adipose tissue (WAT). Here, spheroids (680 ± 60 μm) comprising adipogenic 3T3-L1 cells encapsulated in 3D matrix were fabricated manually on a 96 well scale. Spheroids were highly characterised for lipid morphology, selected metabolite and adipokine secretion, and gene expression; displaying significant upregulation of certain adipogenic-specific genes compared with a 2D model. Furthermore, induction of lipolysis and promotion of lipogenesis in spheroids could be triggered by exposure to 8-br-cAMP and oleic-acid respectively. Metabolic and high content imaging data of spheroids exposed to an adipose-targeting drug, rosiglitazone, resulted in dose-responsive behavior. Thus, our 3D WAT model has potential as a powerful scalable tool for compound screening and for investigating adipose biology.

中文翻译：

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白色脂肪组织的高通量药物反应模型的开发，包括 3D 基质中的脂肪生成 3T3-L1 细胞。

脂肪模型已应用于代谢疾病（如糖尿病）的机制研究以及随后新疗法的发现。然而，典型模型要么不够复杂（2D 细胞培养），要么昂贵且劳动密集型（小鼠/体内）。为了弥合这些模型之间的差距，并为了更好地为临床前研究提供信息，我们开发了一种药物反应性白色脂肪组织 (WAT) 3D 模型。在这里，包含封装在 3D 基质中的脂肪生成 3T3-L1 细胞的球体 (680 ± 60 μm) 是在 96 孔规模上手动制造的。球体在脂质形态、选定的代谢物和脂肪因子分泌以及基因表达方面具有高度特征；与 2D 模型相比，显示某些脂肪生成特异性基因的显着上调。此外，分别暴露于 8-br-cAMP 和油酸可引发球体中脂肪分解的诱导和脂肪生成的促进。暴露于脂肪靶向药物罗格列酮的球体的代谢和高内涵成像数据导致剂量响应行为。因此，我们的 3D WAT 模型具有作为化合物筛选和脂肪生物学研究的强大可扩展工具的潜力。