9-oxo-10(E),12(E)-octadecadienoic acid derived from tomato is a potent PPAR α agonist to decrease triglyceride accumulation in mouse primary hepatocytes
Article first published online: 18 NOV 2010
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 4, pages 585–593, April 2011
How to Cite
Kim, Y.-I., Hirai, S., Takahashi, H., Goto, T., Ohyane, C., Tsugane, T., Konishi, C., Fujii, T., Inai, S., Iijima, Y., Aoki, K., Shibata, D., Takahashi, N. and Kawada, T. (2011), 9-oxo-10(E),12(E)-octadecadienoic acid derived from tomato is a potent PPAR α agonist to decrease triglyceride accumulation in mouse primary hepatocytes. Mol. Nutr. Food Res., 55: 585–593. doi: 10.1002/mnfr.201000264
- Issue published online: 4 APR 2011
- Article first published online: 18 NOV 2010
- Manuscript Accepted: 23 SEP 2010
- Manuscript Revised: 10 SEP 2010
- Manuscript Received: 9 JUN 2010
- Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Kyoto University, Kyoto, Japan
- Division of Food Function and Chemistry, Research Institute for Production Development, Kyoto, Japan
- Primetech Corp., Tokyo, Japan
- Research and Development Program for New Bio-industry Initiatives, Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan. Grant Numbers: 22228001, 22380075
- Fatty acid oxidation;
Scope: Tomato is one of the most common crops worldwide and contains many beneficial compounds that improve abnormalities of lipid metabolism. However, the molecular mechanism underlying the effect of tomato on lipid metabolism is unclear. It has been commonly accepted that peroxisome proliferator-activated receptor α (PPARα) is one of the most important targets for ameliorating abnormalities of lipid metabolism. Therefore, we focused on the activation of PPARα and attempted to detect active compounds activating PPARα in tomato.
Methods and results: To identify such active compounds, we screened fractions of tomato extracts using PPARα luciferase reporter assay. One fraction, rechromatographed-fraction eluted in 57 min (RF57), significantly increased PPARα reporter activity, in which a single compound is detected by LC/MS analysis. On the basis of LC/MS and NMR analyses, we determined the chemical structure of the active compound in RF57 as 9-oxo-10(E),12(E)-octadecadienoic acid (9-oxo-ODA). The RF57 fraction significantly increased the mRNA expression levels of PPARα target genes involved in fatty acid oxidation and O2 consumption in mouse primary hepatocytes. Furthermore, RF57 inhibited cellular triglyceride accumulation in the hepatocytes.
Conclusion: These findings suggest that tomatoes containing 9-oxo-ODA that acts on PPARα are valuable for ameliorating abnormalities of lipid metabolism.