Impact of apolipoprotein E genotype and dietary quercetin on paraoxonase 1 status in apoE3 and apoE4 transgenic mice

Objectives: The aim of the present study was to determine hepatic paraoxonase 1 (PON1) status in response to apoE genotype and dietary quercetin supplementation in mice. Methods and results: ApoE3 and apoE4 transgenic mice were fed semi-synthetic diets without (controls) and with quercetin (2 mg/g diet) for 6 weeks. Hepatic mRNA and protein levels of PON1 were significantly lower in apoE4 as compared to apoE3 mice. Feeding quercetin-enriched diets induced hepatic PON1 gene expression with a tendency for greater induction in apoE3 as compared to apoE4 mice. Furthermore, hepatic mRNA and protein levels of beta-glucuronidase and sulfatase, both enzymes centrally involved in the deconjugation of quercetin conjugates, were lower in apoE4 vs. apoE3 mice. PPAR gamma (which partly controls PON1 gene expression) mRNA levels were lower in apoE4 vs. apoE3 mice. Conclusion: We provide first evidence that PON1 is differentially regulated in response to apoE genotype. (C) 2010 Elsevier Ireland Ltd. All rights reserved.