Modulation of adipose tissue inflammation by FOXP3+Treg cells, IL-10, and TGF-β in metabolically healthy class III obese individuals

Objective: The objective of this study was to compare the profiles of proinflammatory (interleukin [IL]-6 and tumor necrosis factor [TNF]) and anti-inflammatory (IL-10 and transforming growth factor [TGF]-beta) adipokines in the blood, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) of metabolically healthy class III obese individuals and normal-weight controls. Methods: The serum concentrations (enzyme-linked immunosorbent assay [ELISA], mRNA expression levels (reverse transcriptase polymerase chain reaction), and adipose tissue secretion (ELISA) of IL-6, TNF, IL-10, and TGF-beta were analyzed, as were the mRNA expression of FOXP3 (present in regulatory T cells) and the secretion (Western blotting) of matrix metalloproteinases in the adipose tissue. Results: There were no differences in the circulating levels, expression, or secretion of IL-6 and TNF between the groups or tissues. The expression and circulating levels of IL-10 were higher in obese individuals, especially in the SAT. Although the blood concentration of TGF-beta was similar between the groups, its expression and secretion levels were higher in the adipose tissues of obese individuals compared with controls. FOXP3 and MMP expression levels were higher in the SAT and VAT of obese individuals, respectively, compared with the controls. Conclusion: Metabolically healthy, extremely obese individuals have effective immunoregulation to counter chronic obesity-related inflammation through the increased production of the anti-inflammatory cytokines IL-10 and TGF-beta in adipose tissue, especially SAT; the increased presence of FOXP3-positive regulatory T cells; and increases in angiogenesis and adipogenesis induced by TGF-beta and MMPs. These regulatory mechanisms could be important in the delayed onset of metabolic complications, even in extremely obese individuals. (C) 2014 Elsevier Inc. All rights reserved.