title: Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs.
abstract: PPARs regulate the expression of genes for energy metabolism in a ligand-dependent manner. PPARs can influence fatty acid oxidation, the level of circulating triglycerides, glucose uptake and insulin sensitivity. Here, we demonstrate that 5-hydroxyeicosapentaenoic acid (HEPE), 8-HEPE, 9-HEPE, 12-HEPE and 18-HEPE (hydroxylation products of EPA) obtained from methanol extracts of Pacific krill (Euphausia pacifica) can act as PPAR ligands. Two of these products, 8-HEPE and 9-HEPE, enhanced the transcription levels of GAL4-PPARs to a significantly greater extent than 5-HEPE, 12-HEPE, 18-HEPE, EPA, and EPA ethyl-ester. 8-HEPE also activated significantly higher transcription of GAL4-PPARα, GAL4-PPARγ, and GAL4-PPARδ than EPA at concentrations greater than 4, 64, and 64 μM, respectively. We also demonstrated that 8-HEPE increased the expression levels of genes regulated by PPARs in FaO, 3T3-F442A, and C2C12 cells. Furthermore, 8-HEPE enhanced adipogenesis and glucose uptake. By contrast, at the same concentrations, EPA showed weak or little effect, indicating that 8-HEPE was the more potent inducer of physiological effects.
authors.affiliation: Iwate Biotechnology Research Center, Kitakami, Iwate 024-0003, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Eriko
authors.initials: E
authors.lastname: Oshiro
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Mayuka
authors.initials: M
authors.lastname: Hakozaki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kimura
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D015118:Eicosapentaenoic Acid / Q000378:metabolism* / Q000494:pharmacology; D033201:Euphausiacea / Q000737:chemistry*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D005227:Fatty Acids; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D015118:Eicosapentaenoic Acid; D005947:Glucose
keywords: adipogenesis; fatty acid oxidation; glucose uptake; peroxisome proliferator-acitivated receptor