Vaticanol C, a resveratrol tetramer, activates PPARα and PPARβ/δ in vitro and in vivo
- Equal contributors
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
Nutrition & Metabolism 2010, 7:46 doi:10.1186/1743-7075-7-46Published: 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.