NK cells in human visceral adipose tissue contribute to obesity‐associated insulin resistance through low‐grade inflammation

Abstract

Dear Editor, Obesity leads to macrophage infiltration in adipose tissue (AT), causing chronic low-grade inflammation (LGI). This in turn leads to insulin resistance, contributing to F I G U R E 1 NK cells from obese subjects promote inflammatory macrophage polarization and produce increased levels of TNF. A, Bloodderived NK cells from control (n = 6; BMI 24.0 [22.5-26.2] kg/m 2 ; white bars) and obese individuals (n = 8; BMI 41.5 [40.4-47.0] kg/m 2 ; black bars) were isolated and co-cultured with either human monocyte derived macrophages to analyze surface expression of M1 markers (CCR7, CD86, and CD64), or incubated with macrophages that were first polarized to an M2 phenotype and assessed for loss of M2 markers (loss of CD209 and CD206; that is, polarization toward M1). An aggregate total effect of polarization toward an M1 phenotype was calculated (ie, a z-score composed of the individual z-scores of-CD209,-CD206, CCR7, CD86, and CD64). Compared to lean individuals, NK cells from obese individuals induced macrophage polarization toward the M1 phenotype (mean difference 1.08 SD [95% CI 0.06-2.10 SD; * P < .05]). Data are presented as mean ± SEM. B, Intracellular TNF levels were measured in blood-derived NK cells of lean (n = 4) and obese individuals (n = 6) using flow cytometry. Box plot is as follows: black line, median; box edges, first and third quartiles; whiskers, minimum, and maximum of all data. C, Association between CD11B surface expression and intracellular TNF levels of blood-derived NK cells (n = 8). Pearson's correlation coefficient, regression coefficient, and their P-value are reported This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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