US EPA

3859957 

Journal Article 

Abstract 

Perfluorohexanesulfonate and perfluorooctanesulfonate decrease plasma cholesterol and triglycerides in APOE*3Leiden transgenic mice. Indication for a PPARα agonist mechanism 

Pieterman, E; van den Hoek, AM; Havekes, LM; Ehresman, DJ; Chang, S; Butenhoff, JL; Princen, HM; Cohen, LH 

2007 

0 

Atherosclerosis. Supplements
ISSN: 1567-5688
EISSN: 1878-5050 

8 

1 

41 

English 

10.1016/S1567-5688(07)71108-X 

WOS:000247869100162 

Objective: Perfluorinated alkyl sulphonates are fully fluorinated amphiphilic organic molecules with strong surface-tension reducing properties. They are stable to environmental and metabolic degradation. Perfluorooctanesulfonate (PFOS) is widely dispersed in humans, fish-eating wildlife, and surface waters. Toxicological studies in rats and monkeys have shown a reduction in serum cholesterol after treatment with PFOS; however, such reductions have not been observed among exposed workers. In the present study we investigated the mechanistical background of the effect of perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHS) and PFOS on cholesterol and triglyceride metabolism in APOE*3Leiden transgenic mice (a mouse model with a human-like lipoprotein profile).

Methods and Results: Whereas PFBS treatment (30 mg/kg/day) had no effect, both PFHS (6 mg/kg/day) and PFOS (3 mg/kg/day) reduced plasma cholesterol (-36% and -31%) and triglycerides (-50% and -22%) in APOE*3Leiden mice, by a decrease in VLDL/IDL, and caused a concomitant shift of HDL towards larger particles. Mice treated for 10 weeks with PFHS and PFOS had increased ALAT levels (2-5 fold), enlarged livers (2-3 fold) and reduced cholesterol 7-α-hydroxylase activities (-60% and -77%) with a decreased fecal excretion of bile acids (-25% and -48%). Furthermore, PFHS and PFOS showed elevated plasma ketone bodies (2-3 fold), decreased respiratory exchange ratios, increased amounts of liver mitochondria and loss of perigonadal fat, all indicative of an increased fatty acid oxidation.

Conclusions: Treatment of APOE*3Leiden mice with PFHS and PFOS results in reduced plasma cholesterol and triglycerides, increased liver size, decreased cholesterol 7-α-hydroxylase and increased fatty acid oxidation, suggesting a PPARα agonist activity. 

76th Congress of the European Atherosclerosis Society 

Helsinki, Finland 

June 10-13, 2007