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The Association of Lipoprotein Lipase and Phosphatidylinositol 3‐Kinase with Macrophage Lipid Accumulation
Author(s) -
Courage Emily,
Fitzpatrick Madeline,
Elliott Ryan,
Yang Yanbo,
Brown Robert
Publication year - 2015
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.29.1_supplement.885.26
Subject(s) - phosphatidylinositol , lipoprotein lipase , macrophage , lipase , kinase , chemistry , association (psychology) , biochemistry , enzyme , psychology , in vitro , psychotherapist
Lipoprotein lipase (LPL) is an extracellular enzyme that hydrolyzes triglycerides and phospholipids within lipoproteins. LPL is expressed in several tissues, including macrophages within atherosclerotic lesions, where it has been shown to promote foam cell formation. Our laboratory previously showed that the hydrolysis products generated by LPL from total lipoproteins, and specifically the free fatty acids (FFA), increased the phosphorylation of the signaling molecule protein kinase B (or Akt). Thus, we hypothesized that the FFA liberated from total lipoproteins by LPL promote lipid accumulation in macrophages in part through a mechanism associated with the phosphatidylinositol 3‐kinase (PI3K) signaling pathway. To test this hypothesis, THP‐1 macrophages were incubated with a mixture of purified FFA (which matched the concentrations of the FFA species liberated by LPL lipoprotein hydrolysis) for 18 hours in the absence or presence of the PI3K inhibitor LY294002. As expected, Oil Red O staining showed an increased cellular accumulation of lipids following the FFA mixture treatment. THP‐1 macrophages in the presence of both the FFA mixture and LY294002 exhibited a 20% decrease of Oil Red O staining (n=9, p<0.0001). However, no differences in Oil Red O staining were observed between THP‐1 macrophages incubated with individual species of FFA in the absence or presence of LY294002, thus suggesting that multiple FFA species together are necessary to modulate the PI3K signaling pathway. Overall, our data show that the FFA mixture indeed promotes macrophage lipid accumulation partially through a PI3K pathway. Funded by the Natural Sciences and Engineering Research Council of Canada (grant #402185/2011).