Estudios científicos
Vaticanol C, a resveratrol tetramer, activates PPARalpha and PPARbeta/delta in vitro and in vivo
Abstract:
ABSTRACT: BACKGROUND: Appropriate long-term drinking of red wine is associated with a reduced risk of cardiovascular disease. Resveratrol, a well-known SIRT1 activator is considered to be one of the beneficial components contained in red wine, and also developed as a drug candidate. We previously demonstrated that resveratrol protects brain against ischemic stroke in mice through a PPARalpha-dependent mechanism. Here we report the different effects of the oligomers of resveratrol. METHODS: We evaluated the activation of PPARs by epsilon-viniferin, a resveratrol dimer, and vaticanol C, a resveratrol tetramer, in cell-based reporter assays using bovine arterial endothelial cells, as well as the activation of SIRT1. Moreover, we tested the metabolic action by administering vaticanol C with the high fat diet to wild-type and PPARalpha-knockout male mice for eight weeks. RESULTS: We show that vaticanol C activates PPARalpha and PPARbeta/delta in cell-based reporter assays, but does not activate SIRT1. Epsilon-Viniferin shows a similar radical scavenging activity as resveratrol, but neither effects on PPARs and SIRT-1. Eight-week intake of vaticanol C with a high fat diet upregulates hepatic expression of PPARalpha-responsive genes such as cyp4a10, cyp4a14 and FABP1, and skeletal muscle expression of PPARbeta/delta-responsive genes, such as UCP3 and PDK4 (pyruvate dehydrogenase kinase, isoform 4), in wild-type, but not PPARalpha knockout mice. CONCLUSION: Vaticanol C, a resveratrol tetramer, activated PPARalpha and PPARbeta/delta in vitro and in vivo. These findings indicate that activation of PPARalpha and PPARbeta/delta by vaticanol C may be a novel mechanism, affording beneficial effects against lifestyle-related disease.
Comentarios divulgativos:
Una apropiada y moderada ingesta de vino tinto esta asociada con una reducción del riesgo de padecer enfermedades coronarias. El resveratrol el cual es un conocido activador del compuesto SIRT1, esta considerado como uno de los componentes presentes en el vino más beneficiosos y es un candidato a ser desarrollado como medicamento. Los autores de este estudio previamente demostraron que el resveratrol protege el cerebro contra ataques isquémicos en ratones a través del mecanismo denominado PPARalpha. En este estudio se muestran los diferentes efectos de los oligomeros del resveratrol. El compuesto Vaticanol C el cual es un tetrámero del resveratrol activa PPARbeta/delta tanto in vivo como in vitro. Tal vez el vaticanol C pueda ser un novedoso mecanismo que aporte efectos beneficiosos frente a algunas enfermedades.
