Xie Linjun, Zou Liying, Chen Jie, Liu Youxue
Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Nutrition and Health, Chongqing, China.
Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
Int J Endocrinol. 2020 Jan 31;2020:6525787. doi: 10.1155/2020/6525787. eCollection 2020.
Obesity, caused by an increased number and volume of adipocytes, is a global epidemic that seriously threatens human health. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into adipocytes. All-trans retinoic acid (atRA, the active form of vitamin A) inhibits the adipogenic differentiation of BMSCs through its receptor RARG. The expression level of FRA1 (FOS like 1, AP-1 transcription factor subunit) in atRA-treated BMSCs increased, suggesting that atRA-mediated inhibition of BMSCs adipogenesis involves FRA1. BMSCs were transfected with adenovirus overexpressing (ad-fra1) or silenced for (si-fra1) and then treated with atRA. BMSCs treated with atRA and treated with ad-fra1 showed decreased mRNA and protein levels of key adipogenic genes (, ) and adipogenesis-associated genes (, , , and ); atRA had a stronger inhibitory effect on adipogenesis compared with that in the ad-fra1 group. Adipogenic gene expression in -silenced BMSCs was significantly upregulated. Compared with that in the atRA group, the si-fra1 + atRA also upregulated adipogenic gene expression. However, compared with si-fra1, si-fra1 + atRA significantly inhibited adipogenic differentiation. Chromatin immunoprecipitation showed that RARG directly regulates and FRA1 directly regulates and . The results supported the conclusion that atRA inhibits BMSC adipogenesis partially through the RARG-FRA1-PPARG2 or the CEBPA axis or both. Thus, vitamin A might be used to treat obesity and its related diseases.
肥胖是一种由脂肪细胞数量和体积增加引起的全球性流行病，严重威胁人类健康。骨髓间充质干细胞（BMSCs）可分化为脂肪细胞。全反式维甲酸（atRA，维生素A的活性形式）通过其受体RARG抑制BMSCs的成脂分化。在atRA处理的BMSCs中，FRA1（FOS样蛋白1，AP-1转录因子亚基）的表达水平升高，提示atRA介导的BMSCs成脂抑制作用涉及FRA1。用过表达（ad-fra1）或沉默（si-fra1）的腺病毒转染BMSCs，然后用atRA处理。用atRA处理并同时用ad-fra1处理的BMSCs显示关键成脂基因（ ， ）和成脂相关基因（ ， ， ，和 ）的mRNA和蛋白质水平降低；与ad-fra1组相比，atRA对成脂的抑制作用更强。沉默FRA1的BMSCs中成脂基因表达显著上调。与atRA组相比，si-fra1 + atRA也上调了成脂基因表达。然而，与si-fra1相比，si-fra1 + atRA显著抑制了成脂分化。染色质免疫沉淀显示RARG直接调控 ，FRA1直接调控 和 。结果支持了atRA部分通过RARG-FRA1-PPARG2或CEBPA轴或两者抑制BMSCs成脂的结论。因此，维生素A可能用于治疗肥胖及其相关疾病。
