RRC ID 44987
Author Yamada H, Oshiro E, Kikuchi S, Hakozaki M, Takahashi H, Kimura K.
Title Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs.
Journal J Lipid Res
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.
Volume 55(5)
Pages 895-904
Published 2014-5-1
DOI 10.1194/jlr.M047514
PII jlr.M047514
PMID 24668940
PMC PMC3995467
MeSH Adipogenesis / drug effects Angiopoietin-like 4 Protein Angiopoietins / genetics Animals Biological Transport / drug effects Cell Line Eicosapentaenoic Acid / metabolism* Eicosapentaenoic Acid / pharmacology Euphausiacea / chemistry* Fatty Acids / metabolism Glucose / metabolism Humans Ligands Mice Mitochondria / drug effects Mitochondria / metabolism Myoblasts / drug effects Myoblasts / metabolism Oxidation-Reduction Peroxisome Proliferator-Activated Receptors / genetics Peroxisome Proliferator-Activated Receptors / metabolism* Peroxisomes / drug effects Peroxisomes / metabolism Transcriptional Activation / drug effects
IF 4.743
Times Cited 22
Human and Animal Cells