Premium
Fatty acid transport protein 1 mediates macrophage eicosanoid metabolism
Author(s) -
Qin Yuanyuan,
Freemerman Alex Jay,
Li Lei,
Coleman Rosalind,
Galanko Joesh,
Edin Matthew,
Zeldin Darryl,
Stahl Andreas,
Makowski Liza
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.373.5
Subject(s) - eicosanoid , proinflammatory cytokine , inflammation , arachidonic acid , metabolism , fatty acid , biology , eicosanoid metabolism , fatty acid metabolism , lipoxygenase , biochemistry , chemistry , medicine , endocrinology , enzyme , immunology
The fatty acid transport protein (FATP) is expressed in tissues with active lipid metabolism including macrophages (MPs). FATP1 is a long and very long chain fatty acyl‐CoA synthetase (ACS). Preliminary data in RAW264.7 MPs over‐expressing (OE) FATP1 showed increases in ACS activity along with a blunting of proinflammatory mediators compared to empty vector (EV); while FATP−/− bone marrow derived MPs (BMDMs) displayed blunted ACS activity with elevations in IL‐6, TNFα and MCP‐1 compared to FATP+/+. We hypothesize that FATP1 modulates availability of fatty acids as fuel or as substrates for eicosanoid synthesis. We aim to investigate if FATP1 modulates eicosanoid metabolism and inflammation in MPs. MPs were treated with 5ng/mL LPS and 10 ng/ml IFNγ to polarize to the pro‐inflammatory M1 subtype, or left untreated. Liquid chromatography mass spectrometry results showed FATP1‐OE drove statistically significant increases in PGD2, PGF2α, 8isoPGF2α and TXB2, and decreases in proinflammatory 11, 12, 15‐HETEs, vs. EV. FATP1‐OE also had lower levels of AA compared to EV through metabolomics. Complementary to OE, FATP1−/− displayed elevated 8, 11, 12, and 15‐HETEs. Future directions will examine FATP‐1 mediated oxidation of AA and incorporation into lipids in macrophages. In conclusion, FATP‐1 decreases MPs inflammation potentially through regulation of eicosanoid production. AA017376Grant Funding Source : R00 AA017376