Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Clin Hemorheol Microcirc. 2019;71(4):415-424. doi: 10.3233/CH-199005.
Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10°C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10-37°C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1α, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37°C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells.
含脂脂肪细胞在适当的培养条件下可以去分化为成纤维样细胞，这种细胞被称为去分化脂肪（DFAT）细胞。然而，已建立的方案中相对较低的去分化效率限制了它们的广泛应用。在这项研究中，我们发现脂肪细胞可以通过体外周期性暴露于冷（10°C）来促进去分化。通过将细胞在周期性冷却/加热循环（10-37°C）中培养一周，成熟脂肪细胞中的脂滴减少。周期性温度变化导致脂肪生成基因（FABP4、瘦素）下调和与线粒体解偶联相关的基因（UCP1、PGC-1α 和 PRDM16）上调。此外，与在 37°C 下培养的细胞相比，周期性暴露于冷后，去分化的成纤维样细胞中细胞增殖标志物 Ki67 的表达增强。我们的体外模型提供了一种简单有效的促进脂肪分解的方法，可用于提高脂肪细胞向多能性 DFAT 细胞的去分化效率。
