Perfluoroalkyl Sulfonates Cause Alkyl Chain Length-Dependent Hepatic Steatosis and Hypolipidemia Mainly by Impairing Lipoprotein Production in APOE*3-Leiden CETP Mice
Perfluoroalkyl Sulfonates Cause Alkyl Chain Length-Dependent Hepatic Steatosis and Hypolipidemia Mainly by Impairing Lipoprotein Production in APOE*3-Leiden CETP Mice
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DOI：
10.1093/toxsci/kfr142
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发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Princen, Hans M. G.
中科院分区：
文献类型：
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作者：
Bijland, Silvia;Rensen, Patrick C. N.;Princen, Hans M. G.
全氟丁烷磺酸盐（PFBS）、全氟己烷磺酸盐（PFHxS）和全氟辛烷磺酸盐（PFOS）是稳定的全氟烷基磺酸盐（PFAS）表面活性剂，PFHxS和PFOS在人体生物监测研究中经常被检测到。一些流行病学研究表明，血清中的全氟辛烷磺酸与非高密度脂蛋白胆固醇（C）之间存在适度的正相关。本研究探讨了PFAS表面活性剂对脂蛋白代谢影响的机制。APOE*3-Leiden.CETP小鼠喂食含有全氟BS、PFHxS或全氟辛烷磺酸（分别为30、6和3毫克/千克/天）的西式饮食4-6周。全氟辛烷磺酸仅适度降低了血浆甘油三酯，而全氟辛烷磺酸和全氟辛烷磺酸则显著降低了甘油三酯、非高密度脂蛋白胆固醇和高密度脂蛋白胆固醇。极低密度脂蛋白（VLDL）的降低是由脂蛋白脂肪酶介导的VLDL-TG清除增强以及VLDL-TG和VLDL-载脂蛋白B产生减少引起的。与载脂蛋白AI合成减少相关的HDL产生减少导致HDL降低。PFHxS和PFOS增加肝脏重量和肝脏TG含量。肝脏基因表达谱数据表明，这些影响是过氧化物酶体增殖物激活受体α和胆甾烷X受体激活的综合结果。总之，PFAS影响脂蛋白代谢的效力随着烷基链长度的增加而增加。全氟辛烷磺酸和全氟辛烷磺酸主要通过损害脂蛋白的生成来降低血浆甘油三酯和总胆固醇，这意味着报告的血清全氟辛烷磺酸和非高密度脂蛋白胆固醇之间的正相关性是关联性的，而不是因果关系。
Perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) are stable perfluoroalkyl sulfonate (PFAS) surfactants, and PFHxS and PFOS are frequently detected in human biomonitoring studies. Some epidemiological studies have shown modest positive correlations of serum PFOS with non-high-density lipoprotein (HDL)-cholesterol (C). This study investigated the mechanism underlying the effect of PFAS surfactants on lipoprotein metabolism. APOE*3-Leiden.CETP mice were fed a Western-type diet with PFBS, PFHxS, or PFOS (30, 6, and 3 mg/kg/day, respectively) for 4-6 weeks. Whereas PFBS modestly reduced only plasma triglycerides (TG), PFHxS and PFOS markedly reduced TG, non-HDL-C, and HDL-C. The decrease in very low-density lipoprotein (VLDL) was caused by enhanced lipoprotein lipase-mediated VLDL-TG clearance and by decreased production of VLDL-TG and VLDL-apolipoprotein B. Reduced HDL production, related to decreased apolipoprotein AI synthesis, resulted in decreased HDL. PFHxS and PFOS increased liver weight and hepatic TG content. Hepatic gene expression profiling data indicated that these effects were the combined result of peroxisome proliferator-activated receptor alpha and pregnane X receptor activation. In conclusion, the potency of PFAS to affect lipoprotein metabolism increased with increasing alkyl chain length. PFHxS and PFOS reduce plasma TG and total cholesterol mainly by impairing lipoprotein production, implying that the reported positive correlations of serum PFOS and non-HDL-C are associative rather than causal.