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9-Oxo-10(E),12(Z),15(Z)-Octadecatrienoic Acid Activates Peroxisome Proliferator-Activated Receptor α in Hepatocytes

  • Original Article
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Lipids

Abstract

The peroxisome proliferator-activated receptor (PPAR)α is mainly expressed in the liver and plays an important role in the regulation of lipid metabolism. It has been reported that PPARα activation enhances fatty acid oxidation and reduces fat storage. Therefore, PPARα agonists are used to treat dyslipidemia. In the present study, we found that 9-oxo-10(E),12(Z),15(Z)-octadecatrienoic acid (9-oxo-OTA), which is a α-linolenic acid (ALA) derivative, is present in tomato (Solanum lycopersicum) extract. We showed that 9-oxo-OTA activated PPARα and induced the mRNA expression of PPARα target genes in murine primary hepatocytes. These effects promoted fatty acid uptake and the secretion of β-hydroxybutyrate, which is one of the endogenous ketone bodies. We also demonstrated that these effects of 9-oxo-OTA were not observed in PPARα-knockout (KO) primary hepatocytes. To our knowledge, this is the first study to report that 9-oxo-OTA promotes fatty acid metabolism via PPARα activation and discuss its potential as a valuable food-derived compound for use in the management of dyslipidemia.

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Abbreviations

9-oxo-OTA:

9-Oxo-10(E),12(Z),15(Z)-Octadecatrienoic acid

9-oxo-ODA:

9-Oxo-10,12-Octadecadienoic acid

BSA:

Bovine serum albumin

DMEM:

Dulbecco’s modified eagle’s medium

EtOH:

Ethanol

HAD:

cis-10-Heptadecenoic acid

LC–MS:

Liquid chromatography–mass spectrometry

LNA:

Linoleic acid

ALA:

α-Linolenic acid

PBS:

Phosphate-buffered saline

PPAR:

Peroxisome proliferator-activated receptor

QTOFMS:

Quadrupole-time-of-flight MS

UPLC:

Ultra performance LC

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Acknowledgments

The authors thank S. Shinoto and M. Sakai for secretarial and technical support, respectively. This work was supported in part by Research and Development Projects for Application in Promoting New Policies Agriculture, Forestry, and Fisheries of Japan, by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (22228001 and 24688015), and by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (24521).

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Authors and Affiliations

  1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan

    Haruya Takahashi, Kosuke Kamakari, Tsuyoshi Goto, Hideyuki Hara, Shinsuke Mohri, Nobuyuki Takahashi & Teruo Kawada

  2. Research Unit for Physiological Chemistry, Kyoto University, Kyoto, 606-8501, Japan

    Tsuyoshi Goto, Nobuyuki Takahashi & Teruo Kawada

  3. Kazusa DNA Research Institute, Chiba, 292-0818, Japan

    Hideyuki Suzuki & Daisuke Shibata

  4. Department of Food Science and Nutrition, Nara Women’s University, Nara, 630-8506, Japan

    Rieko Nakata & Hiroyasu Inoue

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  1. Haruya Takahashi
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Correspondence to Teruo Kawada.

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Takahashi, H., Kamakari, K., Goto, T. et al. 9-Oxo-10(E),12(Z),15(Z)-Octadecatrienoic Acid Activates Peroxisome Proliferator-Activated Receptor α in Hepatocytes. Lipids 50, 1083–1091 (2015). https://doi.org/10.1007/s11745-015-4071-3

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