Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties.
n-3 PUFAs have beneficial health effects which are believed to be partly related to their anti-inflammatory properties, however the exact mechanisms behind this are unknown. One possible explanation could be via their conversion to N-acyl ethanolamines (NAEs), which are known to possess anti-inflammatory properties. Using fatty acid precursors we showed that 3T3-L1 adipocytes are indeed able to convert docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to their NAE derivatives docosahexaenoyl ethanolamine (DHEA) and eicosapentaenoyl ethanolamine (EPEA), respectively. This synthesis took place on top of an apparent background formation of these NAEs in standard culture medium. In addition we were able to demonstrate the presence of DHEA, but not of EPEA, in human plasma. DHEA and EPEA were found to decrease LPS induced adipocyte IL-6 and MCP-1 levels. Results of combined incubations with PPAR-gamma and CB2 antagonists suggest a role of these receptors in mediating the reduction of IL-6 by DHEA. Our results are in line with the hypothesis that in addition to other pathways, formation of N-acyl ethanolamines may contribute to the biological activity of n-3 PUFAs. Different targets, including the endocannabinoid system, may be involved in the immune-modulating activity of these "fish-oil-derived NAEs."
Balvers
Michiel G J
MG
Business Unit Quality & Safety, TNO Quality of Life, PO Box 360, 3700 AJ Zeist, The Netherlands. michiel.balvers@tno.nl
Verhoeckx
Kitty C M
KC
Plastina
Pierluigi
P
Wortelboer
Heleen M
HM
Meijerink
Jocelijn
J
Witkamp
Renger F
RF
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D003470:Culture Media; D004281:Docosahexaenoic Acids / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004983:Ethanolamines / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D013058:Mass Spectrometry; D051379:Mice
D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003470:Culture Media; D004983:Ethanolamines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid