Vaticanol C, a resveratrol tetramer, activates PPARalpha and PPARbeta/delta in vitro and in vivo

• Published in: Nutrition & metabolism Vol. 7; p. 46
• Main Authors: Tsukamoto, Tomoko, Nakata, Rieko, Tamura, Emi, Kosuge, Yukiko, Kariya, Aya, Katsukawa, Michiko, Mishima, Satoshi, Ito, Tetsuro, Iinuma, Munekazu, Akao, Yukihiro, Nozawa, Yoshinori, Arai, Yuji, Namura, Shobu, Inoue, Hiroyasu
• Format: Journal Article
• Language: English
• Published: England 27.05.2010
• ISSN: 1743-7075
• DOI: 10.1186/1743-7075-7-46

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. 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. 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. 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 diseases.