Elevated adipose tissue associated IL-2 expression in obesity correlates with metabolic inflammation and insulin resistance

Shihab Kochumon,Rasheed Ahmad,Fahd Al-Mulla,Sardar Sindhu,Fatema Al-Rashed,Ashraf Al Madhoun,Ebaa Al-Ozairi,Reeby Thomas

doi:10.1038/s41598-020-73347-y

Shihab Kochumon, Rasheed Ahmad + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-73347-y

Copy DOI

Journal: Scientific Reports	Publication Date: Oct 1, 2020
Citations: 49	License type: open-access

Affiliation: Dasman Diabetes Institute, Ministry of Health

Abstract

Adipose tissue (AT) associated cytokines are involved in the development of chronic low-grade inflammation in obese individuals. IL-2, a pleiotropic cytokine, contributes to immune alterations during inflammation. However, the interaction between AT-IL-2 and other inflammatory biomolecules in obesity remains elusive. We investigated whether AT-IL-2 expression was associated with markers of inflammation and insulin resistance in overweight/obese individuals. Subcutaneous fat tissues were collected from 56 individuals (lean/overweight/obese) for RNA extraction. IL-2 and inflammatory mediators were quantified by qRT-PCR and immunohistochemistry. CRP was measured by ELISA. AT-IL-2 expression was higher in obese compared with lean individuals (P < 0.021) and correlated with BMI. IL-2 correlated with interleukins IL-8 and IL-12A (r = 0.333–0.481; p = 0.0001–0.029); as well as with chemokines and their receptors including CCL5, CCL19, CCR2 and CCR5 (r = 0.538–0.677; p < 0.0001). Moreover, IL-2 correlated with toll-like receptors (TLR2, TLR8, TLR10), interferon regulatory factor 5 (IRF5) and cluster of differentiation CD11c (r = 0.282–0.357; p < 0.039). Notably, IL-2 was associated positively with fasting blood glucose (FBG), HbA1c, TGL and CRP (r ≥ 0.423;P ≤ 0.007). In multiple regression analysis, IL-2 is an independent predictor of IL-8, IL-12A, TLR10, TGL and HbA1c. Overall, our data demonstrate that increased expression of the AT-IL-2, in obesity, may represent a novel biomarker for progression of metabolic inflammation and insulin-resistance.

Highlights

The prevalence of obesity is increasing dramatically, and nearly two third of the of global population is either overweight or o bese[1, 2]
We report that adipose tissue IL-2 gene/protein expression was upregulated in obese individuals compared to lean individuals
Mean values for total plasma cholesterol and low-density lipoproteins (LDL) levels were comparable between three groups, high-density lipoproteins (HDL) was significantly higher in lean individuals (Table 1)

Summary

Introduction

The prevalence of obesity is increasing dramatically, and nearly two third of the of global population is either overweight or o bese[1, 2]. The various leukocyte populations produce and secrete cell type-specific inflammatory mediators that play a key role in the crosstalk among heterogeneous effector cell populations within the obese A T18, 19. IL-2 exerts pleiotropic effects on the immune system and target tissues It plays a crucial role in regulating immune cell proliferation, activation and homoeostasis; well-reviewed elsewhere[23, 24]. We report that adipose tissue IL-2 gene/protein expression was upregulated in obese individuals compared to lean individuals. This elevation of IL-2 is associated with insulin resistance as well as with several important inflammatory markers. In our obese cohort, two diverse clusters of IL-2 gene expression were identified and in those with high expression, IL-2 gene expression correlated positively with fasting blood glucose (FBG) and glycated hemoglobin (Hb1Ac)

Methods

Results

Conclusion