Resveratrol supplementation worsen the dysregulation of genes involved in hepatic lipid homeostasis observed in hyperhomocysteinemic mice.
Hyperhomocysteinemia is characterized by an increase of plasma homocysteine, a thiol-containing amino acid produced during methionine metabolism. Hyperhomocysteinemia has often been associated with coronary artery disease, vascular thrombosis and the development of premature atherosclerosis. We have recently demonstrated that the supplementation of catechin, a polyphenol found in the red wine, significantly reduced plasma homocysteine level in cystathionine beta synthase (CBS) deficient mice, a murine model of hyperhomocysteinemia. In the present study, we have investigated the influence of another well-studied polyphenol found in red wine, resveratrol, on hyperhomocysteinemia. After two months on high methionine diet, heterozygous Cbs deficient mice were administrated the resveratrol in drinking water (0.001%) for one month. High methionine diet significantly increased serum homocysteine levels, and decreased the serum activity of HDL-associated enzyme paraoxonase-1. Chronic administration of resveratrol significantly increased plasma homocysteine level, which was associated with a decreased serum paraoxonase-1 activity, in hyperhomocysteinemic mice. Then we looked at gene expression of several proteins involved in HDL stability and found a down-regulation of lecithin:cholesterol acyltransferase. In conclusion, we found a deleterious effect of resveratrol onto homocysteine and HDL metabolism in a murine model of hyperhomocysteinemia.
Noll
Christophe
C
Université Paris Diderot-Paris 7, Case 7104, 2 Place Jussieu, 75251 Paris Cedex 05, EA 3508, Paris, France.
Hamelet
Julien
J
Ducros
Véronique
V
Belin
Nicole
N
Paul
Jean-Louis
JL
Delabar
Jean-Maurice
JM
Janel
Nathalie
N
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects*; D005838:Genotype; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D000077185:Resveratrol; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
D016632:Apolipoprotein A-I; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013267:Stilbenes; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D003541:Cystathionine beta-Synthase; D000077185:Resveratrol