Biochemical and Biophysical Research Communications, Vol.482, No.4, 849-856, 2017
Activation of PPAR gamma does not contribute to macrophage ABCA1 expression and ABCA1-mediated cholesterol efflux to apoAI
Activation of macrophage ABCAI/G1 expression and cholesterol efflux is believed one of the mechanisms by which PPAR gamma inhibits atherosclerosis. PPAR gamma can also activate CD36 expression, a receptor for oxLDL, which may supply LXR ligands to activate LXR-ABCA1/G1 pathways. However, the controversial effects of PPAR gamma on ABCA1 expression have been reported. In this study, we used peritoneal macrophages isolated from wild type and CD36 deficient (CD36) mice to clarify if PPAR gamma ligands can influence ABCA1 expression by CD36 function. We found that CD36 deficiency had no effect on cholesterol efflux and ABCAI/ABCG1 expression at basal levels. In both cell types, PPAR gamma ligands (15d-PGJ2, troglitazone and pioglitazone) reduced ABCA1 expression and ABCA1-mediated cholesterol efflux to apoAI, with most by troglitazone. LXR ligand-induced ABCA1 expression and cholesterol efflux was attenuated by PPAR gamma ligands. Associated with decreased ABCA1 protein levels, ABCA1 mRNA and promoter activity were reduced by PPAR gamma ligands. Furthermore, high expressing PPARy reduced ABCA1 expression and LXR-activated ABCA1 promoter in a CD36-independent manner. In contrast, ABCG1 expression was induced by PPAR gamma ligands while inhibited by PPAR gamma inactivation. Taken together, our study suggests that enhancement of macrophage cholesterol metabolism by PPAR gamma is not contributed by activating ABCA1 expression and ABCA1-mediated cholesterol efflux to apoAI, which is not involved by CD36 expression either. (C) 2016 Elsevier Inc. All rights reserved.