PPARgamma1 and LXRalpha face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1.
Peroxisome proliferator-activated receptor gamma1 (PPARgamma1) and liver X receptor alpha (LXRalpha) are nuclear receptors that play pivotal roles in macrophage cholesterol homeostasis and inflammation; key biological processes in atherogenesis. The activation of PPARgamma1 and LXRalpha by natural or synthetic ligands results in the transactivation of ABCA1, ABCG1, and ApoE; integral players in cholesterol efflux and reverse cholesterol transport. In this review, we describe the structure, isoforms, expression pattern, and functional specificity of PPARs and LXRs. Control of PPARs and LXRs transcriptional activity by coactivators and corepressors is also highlighted. The specific roles that PPARgamma1 and LXRalpha play in inducing macrophage cholesterol efflux mediators and antagonizing macrophage inflammatory responsiveness are summarized. Finally, this review focuses on the recently reported regulatory functions that adipocyte enhancer-binding protein 1 (AEBP1) exerts on PPARgamma1 and LXRalpha transcriptional activity in the context of macrophage cholesterol homeostasis and inflammation.
Majdalawieh
Amin
A
American University of Sharjah, Sharjah, United Arab Emirates. amajdalawieh@aus.edu
Ro
Hyo-Sung
HS
D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism*; D002467:Cell Nucleus / Q000276:immunology; D002784:Cholesterol / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D000071518:Liver X Receptors; D008264:Macrophages / Q000276:immunology*; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*
C484818:AEBP1 protein, human; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012097:Repressor Proteins; D002784:Cholesterol; D002268:Carboxypeptidases