Paradoxical effects of the epigenetic modifiers 5-aza-deoxycytidine and suberoylanilide hydroxamic acid on adipogenesis
Paradoxical effects of the epigenetic modifiers 5-aza-deoxycytidine and suberoylanilide hydroxamic acid on adipogenesis
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DOI：
10.1016/j.diff.2019.02.003
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发表时间：
2019-03-01
期刊：
影响因子：
2.9
通讯作者：
Khan, Amir A.
中科院分区：
文献类型：
--
作者：
El-Serafi, Ahmed T.;Sandeep, Divyasree;Khan, Amir A.
脂肪生成是一个重要的生物学过程，与肥胖和代谢紊乱有关。另一方面，脂肪再生作为乳房切除术或严重烧伤后的恢复方法至关重要。此外，优化脂肪形成的体外模型，除了发育研究之外，这将有助于了解脂溶性药物和抗肥胖药物可能的作用和/或副作用。表观遗传是影响细胞分化和定型的重要因素。本研究旨在探讨DNA甲基化和组蛋白去乙酰化酶抑制剂5-氮杂脱氧胞苷（5-Aza-dC）和琥珀酰苯胺异羟肟酸（SAHA）对成脂分化过程的影响。根据我们先前公布的方案应用两种修饰剂，然后进行三个循环的经典两步脂肪形成方案。用SAHA预处理的细胞显示出许多成脂基因的表达增强，包括过氧化物酶体增殖物激活受体-γ以及细胞质内脂肪的积累，如油红和尼罗红染色所示，以及脂肪因子如MCP-1和IP-10的分泌。相反，5-Aza-dC抑制所有这些标志物。总之，在分化方案中添加报道的SAHA步骤可能会对体外脂肪再生方法的进展产生影响。5-Aza-dC在抑制脂肪生成中的可能作用可能具有临床意义，未来需要进一步表征。
Adipogenesis is an important biological process that is linked to obesity and metabolic disorders. On the other hand, fat regeneration is crucial as a restorative approach following mastectomy or severe burn injury. Furthermore, optimizing an in-vitro model of adipogenesis, which would help in understanding the possible effects and/or side effects of fat-soluble drugs and anti-obesity remedies, in addition to the developmental studies. Epigenetic is an important factor that is involved in cellular differentiation and commitment. This study aimed at investigating the effect of DNA methylation and histone deactylases inhibitors, 5-Aza-deoxycytidine (5Aza-dC) and Suberoylanilide hydroxamic acid (SAHA), on the adipogenic differentiation process. The two modifiers were applied according to our previously published protocol, followed by three cycles of a classical, two-step adipogenesis protocol. The cells pretreated with SAHA showed enhanced expression of the many adipogenic genes, including peroxisome proliferator-activated receptor-gamma as well as the accumulation of intracytoplasmic fat as shown by oil red and Nile red staining and the secretion of adipokines, such as MCP-1 and IP-10. On contrary, 5-Aza-dC inhibited all these markers. In conclusion, adding the reported step with SAHA to the differentiation protocols could have an impact on the progress of the in-vitro fat regenerative approach. The possible role of 5-Aza-dC in the inhibition of adipogenesis can be of clinical interest and will need further characterization in the future.