Estudios científicos

Resveratrol supplementation worsen the dysregulation of genes involved in hepatic lipid homeostasis observed in hyperhomocysteinemic mice.

Abstract:

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

Comentarios divulgativos:

La hiperhomocisteinemia se caracteriza por un aumento de la homocisteína plasmática, un tiol que contienen aminoácidos producidos durante el metabolismo de la metionina. La hiperhomocisteinemia se ha asociado frecuentemente con la enfermedad arterial coronaria, trombosis vascular y el desarrollo de aterosclerosis prematura. Recientemente hemos demostrado que la suplementación de la catequina, un polifenol del vino tinto reduce significativamente los niveles plasmáticos de homocisteína en cistationina (CBS) en ratones deficientes usados como modelo murino de hiperhomocisteinemia. En el presente estudio, hemos investigado la influencia del resveratrol en la hiperhomocisteinemia. Después de dos meses de dieta con dosis de metionina alta se administró a los ratones deficientes Cbs heterocigotos resveratrol en el agua potable (0,001%) durante un mes. La administración de resveratrol aumentó significativamente los niveles plasmáticos de homocisteína lo cual se asoció con una disminución de la paraoxonasa-1 en el suero en ratones hiperhomocisteinémicos. Luego observamos la expresión genética de varias proteínas que participan en la estabilidad del. En conclusión, se encontró un efecto perjudicial del resveratrol en el metabolismo de la homocisteína y el HDL en un modelo murino de hiperhomocisteinemia.