title: Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.
abstract: Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Young-il
authors.initials: YI
authors.lastname: Kim
authors.forename: Shizuka
authors.initials: S
authors.lastname: Hirai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Chie
authors.initials: C
authors.lastname: Ohyane
authors.forename: Haruya
authors.initials: H
authors.lastname: Takahashi
authors.forename: Taneaki
authors.initials: T
authors.lastname: Tsugane
authors.forename: Chiaki
authors.initials: C
authors.lastname: Konishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Shuji
authors.initials: S
authors.lastname: Inai
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iijima
authors.forename: Koh
authors.initials: K
authors.lastname: Aoki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shibata
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus; D005234:Fatty Liver / Q000188:drug therapy*; D008042:Linolenic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D018551:Solanum lycopersicum / Q000737:chemistry*; D051379:Mice; D008820:Mice, Obese; D047493:PPAR alpha / Q000819:agonists*; D014280:Triglycerides / Q000032:analysis* / Q000097:blood
chemical_list: D008042:Linolenic Acids; D047493:PPAR alpha; D014280:Triglycerides; C064441:13-oxo-9,11-octadecadienoic acid