Department of Cell Biology, Center for Research and Advanced Studies (Cinvestav), Mexico City, Mexico.
FEBS Open Bio. 2024 Sep;14(9):1503-1525. doi: 10.1002/2211-5463.13861. Epub 2024 Jul 7.
White adipocytes store energy, while brown and brite adipocytes release heat via nonshivering thermogenesis. In this study, we characterized two murine embryonic clonal preadipocyte lines, EB5 and EB7, each displaying unique gene marker expression profiles. EB5 cells differentiate into brown adipocytes, whereas EB7 cells into brite (also known as beige) adipocytes. To draw a comprehensive comparison, we contrasted the gene expression patterns, adipogenic capacity, as well as carbohydrate and lipid metabolism of these cells to that of F442A, a well-known white preadipocyte and adipocyte model. We found that commitment to differentiation in both EB5 and EB7 cells can be induced by 3-Isobutyl-1-methylxanthine/dexamethasone (Mix/Dex) and staurosporine/dexamethasone (St/Dex) treatments. Additionally, the administration of rosiglitazone significantly enhances the brown and brite adipocyte phenotypes. Our data also reveal the involvement of a series of genes in the transcriptional cascade guiding adipogenesis, pinpointing GSK3β as a critical regulator for both EB5 and EB7 adipogenesis. In a developmental context, we observe that, akin to brown fat progenitors, brite fat progenitors make their appearance in murine development by 11-12 days of gestation or potentially earlier. This result contributes to our understanding of adipocyte lineage specification during embryonic development. In conclusion, EB5 and EB7 cell lines are valuable for research into adipocyte biology, providing insights into the differentiation and development of brown and beige adipocytes. Furthermore, they could be useful for the characterization of drugs targeting energy balance for the treatment of obesity and metabolic diseases.
白色脂肪细胞储存能量,而棕色和米色脂肪细胞通过非颤抖性产热释放热量。在这项研究中,我们描述了两种具有独特基因标记表达谱的小鼠胚胎克隆前体细胞系 EB5 和 EB7。EB5 细胞分化为棕色脂肪细胞,而 EB7 细胞分化为米色(也称为 beige)脂肪细胞。为了进行全面比较,我们对比了这些细胞的基因表达模式、脂肪生成能力以及碳水化合物和脂质代谢,与 F442A(一种著名的白色前体脂肪细胞和脂肪细胞模型)进行了对比。我们发现,EB5 和 EB7 细胞的分化可以通过 3-异丁基-1-甲基黄嘌呤/地塞米松(Mix/Dex)和 Staurosporine/地塞米松(St/Dex)处理来诱导。此外,罗格列酮的给药显著增强了棕色和米色脂肪细胞表型。我们的数据还揭示了一系列基因在指导脂肪生成的转录级联中的参与,指出 GSK3β 是 EB5 和 EB7 脂肪生成的关键调节因子。在发育背景下,我们观察到,与棕色脂肪前体类似,米色脂肪前体在小鼠发育中在 11-12 天妊娠或更早出现。这一结果有助于我们理解胚胎发育过程中脂肪细胞谱系的特化。总之,EB5 和 EB7 细胞系对于研究脂肪细胞生物学非常有价值,为棕色和米色脂肪细胞的分化和发育提供了深入了解。此外,它们对于研究针对能量平衡的药物用于治疗肥胖和代谢性疾病可能具有重要价值。