Differential PPAR γ and δ expression in F4/80hi and F4/80lo adipose tissue macrophages (92.8)

Abstract

Abstract Chronic inflammation and macrophage infiltration into adipose tissue are hallmarks of obesity. The objective of this study was to phenotypically and functionally characterize the subsets of adipose tissue macrophages (ATM). We had previously identified two distinct subsets of ATM based on surface expression of the glycoprotein F4/80. Changes in gene expression were examined on sorted F4/80lo and F4/80hi ATM by quantitative real-time RT-PCR and their phenotype assess by flow cytometry. While F4/80lo macrophages predominate in adipose tissue of lean mice, obesity resulted in increased accumulation of both F4/80lo and F4/80hi ATM. The F4/80hi population consistently expressed greater amounts of CD11c, MHC II, CD49b, and CX3CR1 on its cell surface and produced more TNF-α, MCP-1, and IL-10 than the F4/80lo subset, which contained a distinct Ly6ChiCCR2hi population. Gene expression analyses of the sorted populations showed that only the F4/80lo population produced IL-4, whereas the F4/80hi ATM expressed greater amounts of peroxisome proliferator-activated receptor (PPAR) γ, δ, CD36,TNF-α and toll-like receptor-4. Therefore, both the F4/80lo and F4/80hi ATMs are heterogeneous populations, with the F4/80hi population consisting of classically activated and deactivated macrophages expressing PPAR γ and δ and the F4/80lo population consisting mainly of IL-4-expressing alternatively activated M2 macrophages.