Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs

J Lipid Res. 2014 May;55(5):895-904. doi: 10.1194/jlr.M047514. Epub 2014 Mar 25.


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.

Keywords: adipogenesis; fatty acid oxidation; glucose uptake; peroxisome proliferator-acitivated receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Angiopoietin-like 4 Protein
  • Angiopoietins
  • Angptl4 protein, mouse
  • Fatty Acids
  • Ligands
  • Peroxisome Proliferator-Activated Receptors
  • Eicosapentaenoic Acid
  • Glucose