title: Vaticanol C, a resveratrol tetramer, activates PPARalpha and PPARbeta/delta in vitro and in vivo.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsukamoto
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakata
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Tamura
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kosuge
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kariya
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Katsukawa
authors.affiliation: API research Center, API Co. Ltd., Gifu, 502-0071, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mishima
authors.affiliation: Laboratory of Pharmacognosy, Gifu Pharmaceutical University, Gifu 502-8585, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ito
authors.affiliation: Laboratory of Pharmacognosy, Gifu Pharmaceutical University, Gifu 502-8585, Japan.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Iinuma
authors.affiliation: Gifu International Institute of Biotechnology, Gifu 504-0838, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.affiliation: Gifu International Institute of Biotechnology, Gifu 504-0838, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
authors.affiliation: Department of Bioscience, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA30310-1495, USA.
authors.forename: Shobu
authors.initials: S
authors.lastname: Namura
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara, 630-8506, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inoue