PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation

Ajay Chawla, Yaacov Barak, Laszlo Nagy, Debbie Liao, Peter Tontonoz, Ronald M. Evans

Research output: Contribution to journalArticlepeer-review

Abstract

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is highly expressed in lipid-accumulating macrophages of the coronary artery. In light of this, the wide-spread clinical use of thiazolidinediones (TZDs) in the treatment of type II diabetes raises concerns about the role of PPAR-γ in macrophage function and disease progression. To define the role of PPAR-γ in macrophage biology, we used homologous recombination to create embryonic stem cells that were homozygous for a null mutation in the PPAR-γ gene. We demonstrate here that PPAR-γ is neither essential for nor substantially affects the development of the macrophage lineage both in vitro and in vivo. In contrast, we show it is an important regulator of the scavenger receptor CD36, which has been genetically linked to lipid accumulation in macrophages. Both 15-deoxy-δ12,14prostaglandin J2 and thiazolidinediones have anti-inflammatory effects that are independent of PPAR-γ. We show that PPAR-γ is required for positive effects of its ligands in modulating macrophage lipid metabolism, but that inhibitory effects on cytokine production and inflammation may be receptor independent.

Original languageEnglish (US)
Pages (from-to)48-52
Number of pages5
JournalNature medicine
Volume7
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation'. Together they form a unique fingerprint.

Cite this