title: 8-Hydroxyeicosapentaenoic Acid Decreases Plasma and Hepatic Triglycerides via Activation of Peroxisome Proliferator-Activated Receptor Alpha in High-Fat Diet-Induced Obese Mice.
abstract: PPARs regulate the expression of genes involved in lipid homeostasis. PPARs serve as molecular sensors of fatty acids, and their activation can act against obesity and metabolic syndromes. 8-Hydroxyeicosapentaenoic acid (8-HEPE) acts as a PPAR ligand and has higher activity than EPA. However, to date, the PPAR ligand activity of 8-HEPE has only been demonstrated in vitro. Here, we investigated its ligand activity in vivo by examining the effect of 8-HEPE treatment on high fat diet-induced obesity in mice. After the 4-week treatment period, the levels of plasma and hepatic triglycerides in the 8-HEPE-fed mice were significantly lower than those in the HFD-fed mice. The expression of genes regulated by PPARα was significantly increased in 8-HEPE-fed mice compared to those that received only HFD. Additionally, the level of hepatic palmitic acid in 8-HEPE-fed mice was significantly lower than in HFD-fed mice. These results suggested that intake of 8-HEPE induced PPARα activation and increased catabolism of lipids in the liver. We found no significant differences between EPA-fed mice and HFD-fed mice. We demonstrated that 8-HEPE has a larger positive effect on metabolic syndrome than EPA and that 8-HEPE acts by inducing PPARα activation in the liver.
authors.affiliation: Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
authors.forename: Mayuka
authors.initials: M
authors.lastname: Hakozaki
authors.affiliation: Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Motodate
authors.affiliation: Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Nagahora
authors.affiliation: Department of Molecular and Cellular Pharmacology, Iwate Medical University School of Pharmaceutical Sciences, Shiwa, Iwate 028-3694, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hirose