Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Apr 16:8:e004.
doi: 10.1621/nrs.08004.

PPARgamma1 and LXRalpha face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1

Amin Majdalawieh  1 , Hyo-Sung Ro
Affiliations
Review

PPARgamma1 and LXRalpha face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1

Amin Majdalawieh et al. Nucl Recept Signal. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. PPARγ1 and LXRα are key regulators of macrophage cholesterol homeostasis.
Upon uptake of oxLDL by macrophages, oxysterols are synthesized, which allows activation of PPARγ1 and LXRα. Once activated, PPARγ1 and LXRα not only induce the expression of each other, but they also induce the expression of many ABC transporters, as well as that of ApoE. ABCs and ApoE play integral roles in transferring excess cholesterol to its acceptor, HDL, and this initiates the process of reverse cholesterol transport (RCT). In RCT, excess peripheral cholesterol is scavenged by tissue macrophages, which process cholesterol and transport it to the liver via HDL for excretion.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akiyama T. E., Sakai S., Lambert G., Nicol C. J., Matsusue K., Pimprale S., Lee Y. H., Ricote M., Glass C. K., Brewer H. B., Jr., Gonzalez F. J. Conditional disruption of the peroxisome proliferator-activated receptor γ gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol Cell Biol. 2002;22:2607–19. - PMC - PubMed
    1. Albers M., Blume B., Schlueter T., Wright M. B., Kober I., Kremoser C., Deuschle U., Koegl M. A novel principle for partial agonism of liver X receptor ligands. Competitive recruitment of activators and repressors. J Biol Chem. 2006;281:4920–30. - PubMed
    1. Alleva D. G., Johnson E. B., Lio F. M., Boehme S. A., Conlon P. J., Crowe P. D. Regulation of murine macrophage proinflammatory and anti-inflammatory cytokines by ligands for peroxisome proliferator-activated receptor-γ: counter-regulatory activity by IFN-γ. J Leukoc Biol. 2002;71:677–85. - PubMed
    1. Altilia S., Pisciotta L., Garuti R., Tarugi P., Cantafora A., Calabresi L., Tagliabue J., Maccari S., Bernini F., Zanotti I., Vergani C., Bertolini S., Calandra S. Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 +5G>C mutation in ABCA1 gene. J Lipid Res. 2003;44:254–64. - PubMed
    1. Amri E. Z., Bonino F., Ailhaud G., Abumrad N. A., Grimaldi P. A. Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors. J Biol Chem. 1995;270:2367–71. - PubMed