title: 9-Oxo-10(E),12(Z),15(Z)-Octadecatrienoic Acid Activates Peroxisome Proliferator-Activated Receptor α in Hepatocytes.
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.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan.
authors.forename: Haruya
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kamakari
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan.|Research Unit for Physiological Chemistry, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Mohri
authors.affiliation: Kazusa DNA Research Institute, Chiba, 292-0818, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Kazusa DNA Research Institute, Chiba, 292-0818, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shibata
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: Hiroyasu
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan.|Research Unit for Physiological Chemistry, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 611-0011, Japan. fat@kais.kyoto-u.ac.jp.|Research Unit for Physiological Chemistry, Kyoto University, Kyoto, 606-8501, Japan. fat@kais.kyoto-u.ac.jp.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000818:Animals; D050171:Dyslipidemias / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008042:Linolenic Acids / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D047493:PPAR alpha / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D008042:Linolenic Acids; D047493:PPAR alpha; D012333:RNA, Messenger; D017962:alpha-Linolenic Acid; C062140:9-oxo-10,12,15-octadecatrienoic acid
keywords: Fatty acid metabolism; Hepatocytes; LC–MS; Oxylipin; PPARα