Sex-specific regulation of IL-10 production in human adipose tissue in obesity

Abstract

BackgroundObesity-associated metabolic complications display sexual dimorphism and can be impacted by cytokines. We previously showed that interleukin-10 (IL-10) was upregulated in white adipose tissue (WAT) of obese women with type 2 diabetes (T2D). Whether this pertains to men is unknown. The aim of this study was to compare the impact of obesity and T2D on WAT IL-10 levels in men versus women.MethodsPlasma and subcutaneous WAT biopsies were obtained from 108 metabolically well-characterized individuals. WATIL10expression/secretion and WAT-resident IL-10-secreting macrophage number were measured. Circulating sex hormone levels were correlated to WATIL10expression in 22 individuals and sex hormone effects on macrophageIL10expression were investigatedin vitro.ResultsObese women with T2D showed increasedIL10expression/secretion and IL-10-secreting WAT macrophage number compared to other female groups. This difference was absent in men. Non-obese women and men with T2D showed similar IL-10 levels compared to healthy controls, indicating that T2D alone does not regulate IL-10. Although WATIL10expression correlated with serum estrone (E1) concentrations, recombinant E1 did not affect macrophageIL10expressionin vitro.ConclusionWAT IL-10 levels are higher in women with obesity and T2D, but not in men and this effect is primarily attributed to obesityper se. This is less likely to be driven by circulating sex hormones. We propose that the WAT IL-10 might exert protective effects in obesity-associated chronic inflammation in women which could be one of the contributing factors for the decreased morbidity observed in women during obesity than men.