Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue

TLDR

IL‑8 is secreted by human adipose tissue, and its circulating levels are elevated in obesity, correlating with insulin resistance, atherosclerosis, and cardiovascular disease. The study aimed to compare IL‑8 production and release from paired subcutaneous and visceral adipose tissues and to determine the contributions of whole tissue, isolated adipocytes, and nonfat cells. In vitro experiments were performed on paired SAT and VAT samples, measuring IL‑8 release from whole explants, isolated adipocytes, and nonfat cell fractions. VAT releases IL‑8 at fourfold higher levels than SAT, with IL‑8 mRNA twofold higher, and its production is suppressed by dexamethasone and stimulated 15‑fold by IL‑1β; IL‑8 release from whole SAT explants and nonfat cells correlates strongly with BMI, whereas isolated adipocytes do not, indicating that nonfat cells in adipose tissue drive the obesity‑associated rise in circulating IL‑8.

Abstract

IL-8 is released from human adipose tissue. Circulating IL-8 is increased in obese compared with lean subjects and is associated with measures of insulin resistance, development of atherosclerosis, and cardiovascular disease. We studied 1) the production and release of IL-8 in vitro from paired samples of subcutaneous (SAT) and visceral (VAT) adipose tissue and 2) the production of IL-8 from whole adipose tissue, isolated adipocytes, and nonfat cells of adipose tissue. IL-8 release from VAT was fourfold higher than from SAT ( P < 0.05), and IL-8 mRNA was twofold higher in VAT compared with SAT ( P < 0.01). Dexamethasone (50 nM) attenuated IL-8 production by 50% ( P < 0.05), and IL-1β (2 μg/l) increased IL-8 production up to 15-fold ( P < 0.001). IL-8 release from whole SAT explants correlated with body mass index (BMI; r = 0.78; P < 0.001), as did IL-8 release from nonfat cells ( r = 0.79; P < 0.001). However, no correlation was found between IL-8 release from the fraction of isolated adipocytes and BMI ( r = 0.01). In conclusion, we demonstrated an increased release of IL-8 from VAT compared with SAT. Furthermore, our data suggest that the observed elevation in circulating levels of IL-8 in obese subjects is due primarily to the release of IL-8 from nonfat cells from adipose tissue. The high levels of IL-8 release from human adipose tissue and accumulation of this tissue in obese subjects may account for some of the increase in circulating IL-8 observed in obesity.