Exposure to HBCD promotes adipogenesis both in vitro and in vivo by interfering with Wnt6 expression

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 of Pparγ, 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 block Wnt6 gene 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 of Wnt6 in eWAT. Taking together, our findings firstly revealed that HBCD promotes adipogenesis in vitro and in vivo by specifically inhibiting Wnt6 expression, presumably connecting exposure of HBCD to the development of obesity.