Title
Perfluoroalkyl sulfonates cause alkyl chain length-dependent hepatic steatosis and hypolipidemia mainly by impairing lipoprotein production in APOE*3-leiden CETP mice
Author
Bijland, S.
Rensen, P.C.N.
Pieterman, E.J.
Maas, A.C.E.
van der Hoorn, J.W.
van Erk, M.J.
Havekes, L.M.
van Dijk, K.W.
Chang, S.C.
Ehresman, D.J.
Butenhoff, J.L.
Princen, H.M.G.
Publication year
2011
Abstract
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 Westerntype 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 lowdensity 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. © The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Subject
Life
MSB - Microbiology and Systems Biology MHR - Metabolic Health Research
EELS - Earth, Environmental and Life Sciences
Health
Cholesterol
Lipoprotein
Perfluorooctane sulfonate
PPARa
PXR
Triglyceride
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http://resolver.tudelft.nl/uuid:6dd3edf6-bd63-4c00-8953-2a9666ba7673
DOI
https://doi.org/10.1093/toxsci/kfr142
TNO identifier
436013
ISSN
1096-6080
Source
Toxicological Sciences, 123 (1), 290-303
Document type
article