Exposure to HBCD promotes adipogenesis both in vitro and in vivo by interfering with Wnt6 expression
Exposure to HBCD promotes adipogenesis both in vitro and in vivo by interfering with Wnt6 expression
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暴露于 HBCD 通过干扰 Wnt6 表达促进体外和体内脂肪生成
DOI：
10.1016/j.scitotenv.2019.135917
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发表时间：
2020-02-25
影响因子：
9.8
通讯作者：
Du，Yuguo
中科院分区：
文献类型：
--
作者：
Xie，Xinni;Yu，Caixia;Du，Yuguo
六溴环十二烷（HBCD）是一种广泛使用的溴化阻燃剂，也是一种普遍存在的环境污染物。然而，六溴环十二烷的影响和机制以及肥胖症的形成在很大程度上仍然未知。在这里，我们研究了六溴环十二烷对脂肪形成的影响和潜在机制。我们的研究结果首次揭示了小鼠3 T3-L1和人HPA-V前脂肪细胞暴露于六溴环十二烷后均表现出明显的脂肪生成增强，表现为甘油三酯积累和脂肪生成标记基因表达的增加。六溴环十二烷被进一步确定主要在早期脂肪形成和增加Ppar γ（一种关键的脂肪形成调节因子）的表达过程中发挥作用。有趣的是，六溴环十二烷不影响早期关键事件有丝分裂克隆扩增（MCE）、早期关键因子C/EBPβ的表达和激活。通过RNA测序，进一步证明六溴环十二烷可特异性阻断Wnt 6基因表达，并在脂肪形成的早期阶段抑制Wnt/β-catenin途径。与细胞结果一致，长期接触六溴环十二烷的C57 BL/6雄性小鼠表现出附睾白色脂肪组织（eWAT）增重特别增加、主要脂肪形成基因表达升高以及eWAT中Wnt 6表达下调。综上所述，我们的研究结果首次揭示了六溴环十二烷通过特异性抑制Wnt 6表达促进体外和体内脂肪生成，这可能将六溴环十二烷暴露与肥胖的发生联系起来。
Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant, and a ubiquitous environmental contaminant. However, effects and mechanisms underlying HBCD and the development of obesity remain largely unknown. Here, we investigated the effects and underlying mechanisms of HBCD on adipogenesis. Our results firstly disclosed that both murine 3T3-L1 and human HPA-V preadipocyte exposed to HBCD displayed markedly enhanced adipogenesis, manifesting with increase of triglyceride accumulation and expression of adipogenic marker genes. HBCD was further identified to play roles mainly during early-stage adipogenesis and increased expression ofPparγ, a key adipogenic regulator. Interestingly, HBCD didn't affect early key event mitotic clonal expansion (MCE), expression and activation of early pivotal factor C/EBPβ. In virtue of RNA sequencing, HBCD was further demonstrated to specially blockWnt6gene expression and inhibited the Wnt/β-catenin pathway at an early stage of adipogenesis. Consistent with cellular finding, C57BL/6 male mice chronically exposed to HBCD exhibited specially increased epididymal white adipose tissue (eWAT) weight gain, elevated expression of master adipogenic genes and down-regulated expression ofWnt6in eWAT. Taking together, our findings firstly revealed that HBCD promotes adipogenesisin vitroandin vivoby specifically inhibitingWnt6expression, presumably connecting exposure of HBCD to the development of obesity.