Adipogenic Activity of Oligomeric Hexafluoropropylene Oxide (Perfluorooctanoic Acid Alternative) through Peroxisome Proliferator-Activated Receptor γ Pathway,Environmental Science & Technology

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Adipogenic Activity of Oligomeric Hexafluoropropylene Oxide (Perfluorooctanoic Acid Alternative) through Peroxisome Proliferator-Activated Receptor γ Pathway
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2019-03-01 , DOI: 10.1021/acs.est.8b06978
Chuan-Hai Li _{1,

2} , Xiao-Min Ren ₁ , Liang-Hong Guo _{1,

2,

3}

Affiliation

Hexafluoropropylene oxide trimer acid (HFPO-TA) and hexafluoropropylene oxide dimer acid (HFPO-DA) have been used as perfluorooctanoic acid (PFOA) alternatives in the fluoropolymer industry for years. Their widespread environmental distribution, high bioaccumulation capability, and human exposure have caused great concern. Nevertheless, their potential toxicity and health risk remain largely unknown. In the present study, we compared potential disruption effects of HFPO-TA, HFPO-DA, and PFOA on peroxisome proliferator-activated receptor γ (PPARγ) via the investigation of receptor binding, receptor activity, and cell adipogenesis effects. The receptor binding experiment showed HFPO-TA exhibited 4.8–7.5 folds higher binding affinity with PPARγ than PFOA, whereas HFPO-DA exhibited weaker binding affinity than PFOA. They also showed agonistic activity toward PPARγ signaling pathway in HEK 293 cells in the order of HFPO-TA > PFOA > HFPO-DA. Molecular docking simulation indicated HFPO-TA formed more hydrogen bonds than PFOA, whereas HFPO-DA formed fewer hydrogen bonds than PFOA. HFPO-TA promoted adipogenic differentiation and lipid accumulation in both mouse and human preadipocytes with potency higher than PFOA. Adipogenesis in human preadipocytes is a more sensitive end point than mouse preadipocytes. Collectively, HFPO-TA exerts higher binding affinity, agonistic activity, and adipogenesis activity than PFOA. The potential health risk of HFPO-TA should be of concern.

中文翻译：

通过过氧化物酶体增殖物激活受体γ途径的低聚六氟环氧丙烷（全氟辛酸替代品）的成脂活性

六氟环氧丙烷三聚酸（HFPO-TA）和六氟环氧丙烷二聚酸（HFPO-DA）在氟聚合物行业中已用作全氟辛酸（PFOA）替代品。它们广泛的环境分布，高的生物积累能力和人体暴露引起了人们的极大关注。然而，它们的潜在毒性和健康风险仍然未知。在本研究中，我们通过研究受体结合，受体活性和细胞成脂作用，比较了HFPO-TA，HFPO-DA和PFOA对过氧化物酶体增殖物激活受体γ（PPARγ）的潜在破坏作用。受体结合实验表明，HFPO-TA与PPARγ的结合亲和力比PFOA高4.8-7.5倍，而HFPO-DA与PFOA的结合亲和力弱。他们还显示了对HEK 293细胞中PPARγ信号通路的激动活性，依次为HFPO-TA> PFOA> HFPO-DA。分子对接模拟表明，HFPO-TA形成的氢键比PFOA多，而HFPO-DA形成的氢键比PFOA少。HFPO-TA促进小鼠和人类前脂肪细胞中的脂肪形成分化和脂质蓄积，其效力高于PFOA。与小鼠前脂肪细胞相比，人前脂肪细胞中的脂肪形成是一个更敏感的终点。总体而言，HFPO-TA比PFOA具有更高的结合亲和力，激动活性和成脂活性。HFPO-TA的潜在健康风险值得关注。而HFPO-DA形成的氢键少于PFOA。HFPO-TA促进小鼠和人类前脂肪细胞中的脂肪形成分化和脂质蓄积，其效力高于PFOA。与小鼠前脂肪细胞相比，人前脂肪细胞中的脂肪形成是一个更敏感的终点。总体而言，HFPO-TA比PFOA具有更高的结合亲和力，激动活性和成脂活性。HFPO-TA的潜在健康风险值得关注。而HFPO-DA形成的氢键少于PFOA。HFPO-TA促进小鼠和人类前脂肪细胞中的脂肪形成分化和脂质蓄积，其效力高于PFOA。与小鼠前脂肪细胞相比，人前脂肪细胞中的脂肪形成是一个更敏感的终点。总体而言，HFPO-TA比PFOA具有更高的结合亲和力，激动活性和成脂活性。HFPO-TA的潜在健康风险值得关注。

更新日期：2019-03-02

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