The eicosapentaenoic acid metabolite 15-deoxy-δ(12,14)-prostaglandin J3 increases adiponectin secretion by adipocytes partly via a PPARγ-dependent mechanism

PLoS One. 2013 May 29;8(5):e63997. doi: 10.1371/journal.pone.0063997. Print 2013.

Abstract

The intake of ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA) increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ(12,14)-PGJ3 (15d-PGJ3), a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ)-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s) for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adiponectin / blood
  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Anilides / pharmacology
  • Animals
  • Dietary Fats / administration & dosage
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / metabolism
  • Eicosapentaenoic Acid / pharmacology
  • Epididymis / drug effects
  • Epididymis / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Male
  • Mice
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / metabolism
  • Prostaglandin D2 / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • 2-chloro-5-nitrobenzanilide
  • Adiponectin
  • Anilides
  • Dietary Fats
  • PPAR gamma
  • Eicosapentaenoic Acid
  • Prostaglandin D2

Grants and funding

This work was supported by INSERM, a grant from the French Artery and Heart Foundation, ECOS-Nord program, a grant from Nutrition Lipid Group (GLN), and from the LISA Carnot Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.