Vaticanol C, a resveratrol tetramer, activates PPARα and PPARβ/δ in vitro and in vivo

Author:

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

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 PPARα-dependent mechanism. Here we report the different effects of the oligomers of resveratrol. Methods We evaluated the activation of PPARs by ε-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 PPARα-knockout male mice for eight weeks. Results We show that vaticanol C activates PPARα and PPARβ/δ in cell-based reporter assays, but does not activate SIRT1. ε-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 PPARα-responsive genes such as cyp4a10, cyp4a14 and FABP1, and skeletal muscle expression of PPARβ/δ-responsive genes, such as UCP3 and PDK4 (pyruvate dehydrogenase kinase, isoform 4), in wild-type, but not PPARα-knockout mice. Conclusion Vaticanol C, a resveratrol tetramer, activated PPARα and PPARβ/δ in vitro and in vivo. These findings indicate that activation of PPARα and PPARβ/δ by vaticanol C may be a novel mechanism, affording beneficial effects against lifestyle-related diseases.

Publisher

Springer Science and Business Media LLC

Subject

Nutrition and Dietetics,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)

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