title: Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype.
abstract: 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.
authors.affiliation: Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Parker
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Akiko
authors.initials: A
authors.lastname: Higuchi
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Vita
authors.forename: Noyan
authors.initials: N
authors.lastname: Gokce
authors.forename: Anette Amstrup
authors.initials: AA
authors.lastname: Pedersen
authors.forename: Christoph
authors.initials: C
authors.lastname: Kalthoff
authors.forename: Søren
authors.initials: S
authors.lastname: Tullin
authors.forename: Anette
authors.initials: A
authors.lastname: Sams
authors.forename: Ross
authors.initials: R
authors.lastname: Summer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
mesh_terms: 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
chemical_list: D052242:Adiponectin; D015415:Biomarkers