PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation.
Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT.
Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, 24061, United States. jbassaga@vt.edu
Josep
J
Bassaganya-Riera
Sarah
S
Misyak
Amir J
AJ
Guri
Raquel
R
Hontecillas
D052436:Adipose Tissue, White / Q000276:immunology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002452:Cell Count; D054402:Chemokine CCL1 / Q000378:metabolism; D054414:Chemokine CCL17 / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology* / Q000378:metabolism; D047495:PPAR gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000943:Antigens, Differentiation; D018955:CD36 Antigens; D054402:Chemokine CCL1; D054414:Chemokine CCL17; D016207:Cytokines; D047495:PPAR gamma; C036763:monocyte-macrophage differentiation antigen; D015847:Interleukin-4; D005947:Glucose