Irisin is a newly discovered myokine that secreted from skeletal muscle cells. Several studies showed that irisin involves in thermogenesis and increases the expression of browning markers such as uncoupling protein-1 that in turns induces the conversion of white adipose tissue to brown fat. Resveratrol (Res) and all-trans retinoic acid (ATRA) can also upregulate the expression of thermogenesis genes. In the present study, the effects of single and combined treatments of Res and ATRA on fibronectin type III domain containing 5 (FNDC5) gene expression was explored. The mouse myoblasts, C2C12 cells, were seeded in 6-well plastic plates and cultured in DMEM media. After differentiation, in a pilot study, C2C12 myotubes were treated with different concentrations of Res and ATRA for 12 h. The best result was obtained by treatment of 1and 25 μM of Res and 1 μM of ATRA. Then the main study was continued by single and combined treatment of these compounds at chosen concentration. After treatments, total RNA was extracted from C2C12 cells. Complementary DNA (cDNA) was generated by the cDNA synthesis kit and FNDC5 mRNA expression was evaluated by the real-time PCR method. The FNDC5 gene expression in C2C12 myotubes of alone-treated with 1 μM, 25 μM Res and 10 μM ATRA did not change compared to vehicle group. However, in combination-treated the expression of FNDC5 gene was significantly increased compared to vehicle group. This is the first evidence that Res and ATRA can regulate FNDC5 gene expression in C2C12 myotubes. More investigations are necessary to explore the therapeutic effects of these nutrients in obesity, diabetes, cardiac and neurovascular disease.

中文翻译：

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白藜芦醇和ATRA联合治疗后，C2C12细胞中FNDC5基因表达上调

Irisin是从骨骼肌细胞分泌的一种新发现的肌动蛋白。几项研究表明，鸢尾素参与生热作用并增加了褐变标记物（例如解偶联蛋白1）的表达，而后者又诱导了白​​色脂肪组织向褐色脂肪的转化。白藜芦醇（Res）和全反式维甲酸（ATRA）也可以上调生热基因的表达。在本研究中，探索了Res和ATRA的单一和联合处理对包含5（FNDC5）基因表达的纤连蛋白III型结构域的影响。将小鼠成肌细胞C2C12细胞接种在6孔塑料板上，并在DMEM培养基中培养。分化后，在一项初步研究中，用不同浓度的Res和ATRA处理C2C12肌管12小时。通过处理1和25μM的Res和1μM的ATRA可获得最佳结果。然后，通过在选定浓度下对这些化合物进行单一和组合处理来继续进行主要研究。处理后，从C2C12细胞中提取总RNA。通过cDNA合成试剂盒生成互补DNA（cDNA），并通过实时PCR方法评估FNDC5 mRNA的表达。与媒介物组相比，单独用1μM，25μMRes和10μMATRA处理的C2C12肌管中的FNDC5基因表达没有变化。然而，与媒介物组相比，在联合治疗中，FNDC5基因的表达显着增加。这是Res和ATRA可以调节C2C12肌管中FNDC5基因表达的第一个证据。有必要进行更多的研究，以探索这些营养素对肥胖，糖尿病，