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

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.

Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly

“…Therefore, improved vascular function due to exercise might partly explain the inhibitory effect on this chemokine [ 41 ]. Furthermore, it could be shown that there is a relationship between IL-8 and IL-2 in the overweight [ 42 ], which could be in line with our results. According to this, we observed a decrease in plasma IL-2 levels within both groups.…”

Dietary Glutamic Acid, Obesity, and Depressive Symptoms in Patients With Schizophrenia

“…The effect seen in this group may be due to fewer cardiovascular risk factors contributing to depression in these individuals, resulting in a greater impact regarding dietary glutamic acid consumption. Additionally, as previously discussed, the role of co-occurring conditions such as obesity, which potentially influences differing inflammatory cascades due to epigenomic modulations, may have also impacted this relationship and mask any correlations between glutamic acid consumption and depressive symptomatology in our obese subjects ( 46 , 47 ).…”

“…The effect seen in this group may be due to fewer cardiovascular risk factors contributing to depression in these individuals, resulting in a greater impact regarding dietary glutamic acid consumption. Additionally, as previously discussed, the role of co-occurring conditions such as obesity, which potentially influences differing inflammatory cascades due to epigenomic modulations, may have also impacted this relationship and mask any correlations between glutamic acid consumption and depressive symptomatology in our obese subjects (46,47). Regardless, these relationships should be considered preliminary as future research needs to directly examine the role diet and in particular, MSG consumption on not only depressive symptomatology, and psychotic symptoms in patients with a schizophrenia spectrum diagnosis, but also epigenomic mechanisms behind these potential relationships.…”

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

“…Thus, adipose IRF5 transcripts in obesity correlate positively with TNF-α, IL-1β, IL-6, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP10, CCL2/MCP1, CCL5, and CCL7/MCP3, all of which can be elevated in COVID-19 "cytokine storm" (107, 108); positive correlations with IL-2 and IL-12 have been reported by the same group. TLR4, TLR7, and TLR8 are increased in obesity and correlate with IRF5 expression, but whether this occurs in SARS-CoV-2 infection is unknown (109,110).…”