Perfluoroalkyl Sulfonates Cause Alkyl Chain Length-Dependent Hepatic Steatosis and Hypolipidemia Mainly by Impairing Lipoprotein Production in APOE*3-Leiden CETP Mice

被引:120
作者
Bijland, Silvia [2 ]
Rensen, Patrick C. N. [3 ]
Pieterman, Elsbet J. [1 ]
Maas, Annemarie C. E. [1 ]
van der Hoorn, Jose W. [1 ]
van Erk, Marjan J. [4 ]
Havekes, Louis M. [1 ,3 ,5 ]
van Dijk, Ko Willems [2 ,3 ]
Chang, Shu-Ching [6 ]
Ehresman, David J. [6 ]
Butenhoff, John L. [6 ]
Princen, Hans M. G. [1 ]
机构
[1] Netherlands Org Appl Sci Res Qual Life, Dept Biosci, Gaubius Lab, NL-2301 CE Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Gen Internal Med Endocrinol & Metab Dis, NL-2300 RC Leiden, Netherlands
[4] Netherlands Org Appl Sci Res Qual Life, NL-3700 AJ Zeist, Netherlands
[5] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands
[6] 3M Co, Dept Med, St Paul, MN 55144 USA
关键词
cholesterol; lipoprotein; perfluorooctane sulfonate; PPAR alpha; PXR; triglyceride; LOW-DENSITY-LIPOPROTEIN; ESTER TRANSFER PROTEIN; INCREASES HDL-CHOLESTEROL; SPRAGUE-DAWLEY RATS; TRANSGENIC MICE; PERFLUOROOCTANE SULFONATE; PEROXISOME PROLIFERATION; POTASSIUM PERFLUOROOCTANESULFONATE; LIVER-MICROSOMES; APOLIPOPROTEIN-B;
D O I
10.1093/toxsci/kfr142
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:290 / 303
页数:14
相关论文
共 54 条
[31]   Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers [J].
Olsen, Geary W. ;
Burris, Jean M. ;
Ehresman, David J. ;
Froehlich, John W. ;
Seacat, Andrew M. ;
Butenhoff, John L. ;
Zobel, Larry R. .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2007, 115 (09) :1298-1305
[32]   A comparison of the pharmacokinetics of perfluorobutanesulfonate (PFBS) in rats, monkeys, and humans [J].
Olsen, Geary W. ;
Chang, Shu-Ching ;
Noker, Patricia E. ;
Gorman, Gregory S. ;
Ehresman, David J. ;
Lieder, Paul H. ;
Butenhoff, John L. .
TOXICOLOGY, 2009, 256 (1-2) :65-74
[33]   Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations [J].
Olsen, GW ;
Burris, JM ;
Burlew, MM ;
Mandel, JH .
JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, 2003, 45 (03) :260-270
[34]   VERY FAST ULTRACENTRIFUGATION OF SERUM-LIPOPROTEINS - INFLUENCE ON LIPOPROTEIN SEPARATION AND COMPOSITION [J].
PIETZSCH, J ;
SUBAT, S ;
NITZSCHE, S ;
LEONHARDT, W ;
SCHENTKE, KU ;
HANEFELD, M .
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1995, 1254 (01) :77-88
[35]   Cafestol increases serum cholesterol levels in apolipoprotein E*3-Leiden transgenic mice by suppression of bile acid synthesis [J].
Post, SM ;
de Roos, B ;
Vemeulen, M ;
Afman, L ;
Jong, MC ;
Dahlmans, VEH ;
Havekes, LM ;
Stellaard, F ;
Katan, MB ;
Princen, HMG .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (06) :1551-1556
[36]   Cholesterol 7α-hydroxylase deficiency in mice on an APOE*3-Leiden background impairs very-low-density lipoprotein production [J].
Post, SM ;
Groenendijk, M ;
Solaas, K ;
Rensen, PCN ;
Princen, HMG .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (04) :768-774
[37]   Increased fecal bile acid excretion in transgenic mice with elevated expression of human phospholipid transfer protein [J].
Post, SM ;
de Crom, R ;
van Haperen, R ;
van Tol, A ;
Princen, HMG .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (05) :892-897
[38]   Comparative Analysis of Gene Regulation by the Transcription Factor PPARα between Mouse and Human [J].
Rakhshandehroo, Maryam ;
Hooiveld, Guido ;
Muller, Michael ;
Kersten, Sander .
PLOS ONE, 2009, 4 (08)
[39]   GenePattern 2.0 [J].
Reich, M ;
Liefeld, T ;
Gould, J ;
Lerner, J ;
Tamayo, P ;
Mesirov, JP .
NATURE GENETICS, 2006, 38 (05) :500-501
[40]   Evidence for the involvement of xenobiotic-responsive nuclear receptors in transcriptional effects upon perfluoroalkyl acid exposure in diverse species [J].
Ren, Hongzu ;
Vallanat, Beena ;
Nelson, David M. ;
Yeung, Leo W. Y. ;
Guruge, Keerthi S. ;
Lam, Paul K. S. ;
Lehman-McKeeman, Lois D. ;
Corton, J. Christopher .
REPRODUCTIVE TOXICOLOGY, 2009, 27 (3-4) :266-277