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

Tomoko Tsukamoto1, Rieko Nakata1, Emi Tamura1, Yukiko Kosuge1, Aya Kariya1, Michiko Katsukawa1, Satoshi Mishima2, Tetsuro Ito3, Munekazu Iinuma3, Yukihiro Akao4, Yoshinori Nozawa4, Yuji Arai5, Shobu Namura6 and Hiroyasu Inoue1*

Author Affiliations

1 Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan

2 API research Center, API Co. Ltd., Gifu, 502-0071, Japan

3 Laboratory of Pharmacognosy, Gifu Pharmaceutical University, Gifu 502-8585, Japan

4 Gifu International Institute of Biotechnology, Gifu 504-0838, Japan

5 Department of Bioscience, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan

6 Department of Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA30310-1495, USA

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Nutrition & Metabolism 2010, 7:46  doi:10.1186/1743-7075-7-46

Published: 27 May 2010



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.


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.


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.


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.