Tung Emily W Y, Peshdary Vian, Gagné Remi, Rowan-Carroll Andrea, Yauk Carole L, Boudreau Adéle, Atlas Ella
Environmental Health Science and Research Bureau, Health Canada , Ottawa, Ontario, Canada.
Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
Exposure to flame retardants has been associated with negative health outcomes including metabolic effects. As polybrominated diphenyl ether flame retardants were pulled from commerce, human exposure to new flame retardants such as Firemaster® 550 (FM550) has increased. Although previous studies in murine systems have shown that FM550 and its main components increase adipogenesis, the effects of FM550 in human models have not been elucidated.
The objectives of this study were to determine if FM550 and its components are active in human preadipocytes, and to further investigate their mode of action.
Human primary preadipocytes were differentiated in the presence of FM550 and its components. Differentiation was assessed by lipid accumulation and expression of peroxisome proliferator-activated receptor γ (PPARG), fatty acid binding protein (FABP) 4 and lipoprotein lipase (LPL). mRNA was collected for Poly (A) RNA sequencing and was used to identify differentially expressed genes (DEGs). Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis.
FM550 triphenyl phosphate (TPP) and isopropylated triphenyl phosphates (IPTP), increased adipogenesis in human primary preadipocytes as assessed by lipid accumulation and mRNA expression of regulators of adipogenesis such as PPARγ, CCAAT enhancer binding protein (C/EBP) α and sterol regulatory element binding protein (SREBP) 1 as well as the adipogenic markers FABP4 LPL and perilipin. Poly (A) RNA sequencing analysis revealed potential modes of action including liver X receptor/retinoid X receptor (LXR/RXR) activation, thyroid receptor (TR)/RXR, protein kinase A, and nuclear receptor subfamily 1 group H members activation.
We found that FM550, and two of its components, induced adipogenesis in human primary preadipocytes. Further, using global gene expression analysis we showed that both TPP and IPTP likely exert their effects through PPARG to induce adipogenesis. In addition, IPTP perturbed signaling pathways that were not affected by TPP. https://doi.org/10.1289/EHP1318.
接触阻燃剂与包括代谢影响在内的负面健康结果相关。随着多溴二苯醚阻燃剂退出商业市场，人类对新型阻燃剂如Firemaster® 550（FM550）的接触有所增加。尽管此前在小鼠系统中的研究表明FM550及其主要成分会增加脂肪生成，但FM550在人体模型中的作用尚未阐明。
本研究的目的是确定FM550及其成分在人前脂肪细胞中是否具有活性，并进一步研究其作用模式。
在FM550及其成分存在的情况下使人原代前脂肪细胞分化。通过脂质积累以及过氧化物酶体增殖物激活受体γ（PPARG）、脂肪酸结合蛋白（FABP）4和脂蛋白脂肪酶（LPL）的表达来评估分化情况。收集mRNA用于聚腺苷酸RNA测序，并用于鉴定差异表达基因（DEG）。在Ingenuity通路分析中对DEG进行功能分析。
通过脂质积累以及脂肪生成调节因子如PPARγ、CCAAT增强子结合蛋白（C/EBP）α和固醇调节元件结合蛋白（SREBP）1的mRNA表达，以及脂肪生成标志物FABP4、LPL和围脂滴蛋白评估发现，FM550、磷酸三苯酯（TPP）和异丙基化磷酸三苯酯（IPTP）可增加人原代前脂肪细胞中的脂肪生成。聚腺苷酸RNA测序分析揭示了潜在的作用模式，包括肝X受体/视黄酸X受体（LXR/RXR）激活、甲状腺受体（TR）/RXR、蛋白激酶A以及核受体亚家族1 H组成员激活。
我们发现FM550及其两种成分可诱导人原代前脂肪细胞中的脂肪生成。此外，通过全局基因表达分析我们表明，TPP和IPTP可能都通过PPARG发挥作用以诱导脂肪生成。此外，IPTP扰乱了不受TPP影响的信号通路。https://doi.org/10.1289/EHP1318
Zotero 插件
