Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype.
It is established that the adipocyte-derived cytokine adiponectin protects against cardiovascular and metabolic diseases, but the effect of this adipokine on macrophage polarization, an important mediator of disease progression, has never been assessed. We hypothesized that adiponectin modulates macrophage polarization from that resembling a classically activated M1 phenotype to that resembling alternatively-activated M2 cells. Peritoneal macrophages and the stromal vascular fraction (SVF) cells of adipose tissue isolated from adiponectin knock-out mice displayed increased M1 markers, including tumor necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein-1 and decreased M2 markers, including arginase-1, macrophage galactose N-acetyl-galactosamine specific lectin-1, and interleukin-10. The systemic delivery of adenovirus expressing adiponectin significantly augmented arginase-1 expression in peritoneal macrophages and SVF cells in both wild-type and adiponectin knock-out mice. In culture, the treatment of macrophages with recombinant adiponectin protein led to an increase in the levels of M2 markers and a reduction of reactive oxygen species and reactive oxygen species-related gene expression. Adiponectin also stimulated the expression of M2 markers and attenuated the expression of M1 markers in human monocyte-derived macrophages and SVF cells isolated from human adipose tissue. These data show that adiponectin functions as a regulator of macrophage polarization, and they indicate that conditions of high adiponectin expression may deter metabolic and cardiovascular disease progression by favoring an anti-inflammatory phenotype in macrophages.
Ohashi
Koji
K
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Parker
Jennifer L
JL
Ouchi
Noriyuki
N
Higuchi
Akiko
A
Vita
Joseph A
JA
Gokce
Noyan
N
Pedersen
Anette Amstrup
AA
Kalthoff
Christoph
C
Tullin
Søren
S
Sams
Anette
A
Summer
Ross
R
Walsh
Kenneth
K
D052242:Adiponectin / Q000494:pharmacology*; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D015415:Biomarkers; D019070:Cell Lineage; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D017737:Macrophages, Peritoneal; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D052242:Adiponectin; D015415:Biomarkers