School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala Univeristy, Uppsala, Sweden.
J Expo Sci Environ Epidemiol. 2023 Sep;33(5):757-765. doi: 10.1038/s41370-023-00545-x. Epub 2023 Apr 5.
Perfluoroalkyl substances (PFAS) are man-made chemicals with unique properties that are widely distributed in humans and the environment. Recent studies suggest that PFAS are involved in cholesterol metabolism, however, the mechanisms underlying the associations are poorly understood.
We aimed to evaluate associations of plasma PFAS with detailed lipid and lipoprotein subfractions in an adult population of men and women.
We measured concentrations of cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein subclasses, as well as fatty acid and different phospholipid measures, using serum proton nuclear magnetic resonance (1H-NMR), and four plasma PFAS using liquid chromatography-mass spectrometry (UHPLC-MS/MS). Measurements were available for 493 participants (all aged 50 years, 50% female). Multivariable linear regression was used to estimate the association of four PFAS with 43 different 1H-NMR measures, with adjustment for body mass index (BMI), smoking, education, and physical activity.
We found that perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), but not perfluorohexanesulfonate (PFHxS), concentrations were consistently positively associated with concentrations of cholesterol in lipoprotein subfractions, apolipoproteins, as well as composite fatty acid- and phospholipid profiles. The most consistent associations were found for the relationship of PFAS with total cholesterol in intermediate-density lipoprotein (IDL), across all low-density lipoprotein (LDL) subfractions and small high-density lipoprotein (HDL). Moreover, we found weak to null evidence for an association of any of the measured 13 triglyceride lipoprotein subfractions with PFAS.
Our results suggest that plasma PFAS concentrations are associated with cholesterol in small HDL, IDL and all LDL subfractions, as well as apolipoproteins and composite fatty acid and phospholipid profiles but to a lesser extent with triglycerides in lipoproteins. Our findings draw attention to the need for more detailed measurements of lipids across various lipoprotein subfractions and subclasses in assessing the role of PFAS in lipid metabolism.
By performing an in-depth characterization of circulating cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein, fatty acid, and phospholipid concentrations, this study has expanded upon the limited literature available on the associations of plasma PFAS concentrations beyond clinical routine laboratory testing for lipids.
全氟烷基物质（PFAS）是具有独特性质的人造化学品，广泛分布于人类和环境中。最近的研究表明，PFAS 参与胆固醇代谢，但相关机制尚不清楚。
我们旨在评估成年男性和女性人群中血浆 PFAS 与详细脂质和脂蛋白亚组分的相关性。
我们使用血清质子磁共振（1H-NMR）测量了脂蛋白亚组分、载脂蛋白亚类以及脂肪酸和不同磷脂测量值中的胆固醇和甘油三酯浓度，并使用液相色谱-质谱联用（UHPLC-MS/MS）测量了四种血浆 PFAS 浓度。共纳入了 493 名参与者（年龄均为 50 岁，50%为女性），进行了上述测量。采用多变量线性回归，在调整体重指数（BMI）、吸烟、教育程度和体力活动后，评估了四种 PFAS 与 43 种不同 1H-NMR 测量值的相关性。
我们发现，全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）、全氟癸酸（PFDA）而非全氟己烷磺酸（PFHxS）浓度与脂蛋白亚组分、载脂蛋白以及复合脂肪酸和磷脂谱中的胆固醇浓度呈一致的正相关。PFAS 与所有 LDL 亚组分和小而密的高密度脂蛋白（sdHDL）中中间密度脂蛋白（IDL）的总胆固醇之间的关系最为密切。此外，我们发现任何一种所测量的 13 种甘油三酯脂蛋白亚组分与 PFAS 的相关性均很微弱或不存在。
我们的研究结果表明，血浆 PFAS 浓度与小而密的高密度脂蛋白、IDL 和所有 LDL 亚组分以及载脂蛋白和复合脂肪酸和磷脂谱中的胆固醇有关，但与脂蛋白中的甘油三酯关系较小。我们的研究结果表明，需要更详细地测量各种脂蛋白亚组分和亚类中的脂质，以评估 PFAS 在脂质代谢中的作用。
通过深入研究脂蛋白亚组分、载脂蛋白、脂肪酸和磷脂浓度中的循环胆固醇和甘油三酯，本研究扩展了现有关于血浆 PFAS 浓度与临床常规脂质检测以外的相关性的有限文献。
