Macrophage Endothelial Lipase Expression is Regulated by Fatty Acids and PPAR gamma Expression

Abstract

Macrophages within atherosclerotic lesions highly express endothelial lipase (EL) and PPARγ. We previously demonstrated that a saturated fatty acid (FA), palmitic acid (PA), increased macrophage EL mRNA and protein expression, whereas a n‐3 FA, EPA, inhibited the higher expression induced by LPS and PA. We now explored mechanisms by which EPA, in contrast to PA, lowers EL expression in macrophages. Murine J774 and elicited peritoneal macrophages (PM, from C57BL/6 mice) were cultured with 50–300 μM of EPA or PA for 7–24h in the presence or absence of a PPARγ agonist or antagonist. PPARγ mRNA levels were significantly increased by PA (4 fold, p<0.01), whereas EPA abrogated effects of LPS on increasing PPARγ mRNA. PPARγ mRNA positively correlated with EL mRNA expression in J774 and PM (r=0.339, p<0.05; r=0.428, p<0.01, respectively). PPARγ activation by rosiglitazone (a PPARγ agonist) increased EL mRNA (8 fold, p<0.01) and protein expression (2 fold, p<0.01), whereas GW9662 (a PPARγ antagonist) abrogated the stimulation of both rosiglitazone and PA. EPA blocked the increase of EL expression caused by rosiglitazone. Thus, EL expression closely linked to PPARγ expression, and this macrophage‐derived lipase is regulated by fatty acids, in part, through modifying macrophage PPARγ expression.Grant Funding Source: HL40404