1288-P: Increased Adipose Tissue Expression of IL-23 and Its Association with Inflammation in Individuals with High LDL Cholesterol

Abstract

Obesity induced chronic low-grade inflammation is a central risk factor for the development of metabolic syndrome. It has been well documented that high LDL-c induces inflammation. The proinflammatory cytokine Il-23 plays a pivotal role in the pathogenesis of inflammatory diseases. IL-23 and its relationship with LDL- c has not been reported yet. In this cross-sectional study we investigated whether adipose tissue expression of IL-23 associated with the other inflammatory mediators in individuals with high serum levels of low-density lipoprotein cholesterol (LDL-c) . Subcutaneous adipose samples were collected from 67 individuals and divided into two groups based on their serum LDL-c levels (LDL-c: < 2.9 or ≥2.9 mmol/L) . Expression of IL-23 and inflammatory markers was determined using real-time RT-PCR. Plasma lipid measurements included total cholesterol (TC) , triglyceride (TG) , high-density lipoprotein cholesterol (HDL-c) and LDL-c by standard methods, and serum adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) . Individuals with increased serum levels of LDL-c showed high IL-23 expression levels in adipose tissue (p < 0.011) . AT IL-23 expression was correlated positively with LDL-c (r= 0.39, p < 0.0001) . IL-23 expression levels were positively correlated with macrophage markers (CD11c, CD68, CD86, CD127; (r ≥0.37, p≤ 0.02) , TLRs (TLR8, TLR10; (r ≥ 0.39, p ≤ 0.022) , IRF3 (r= 0.46, p< 0.01) , cytokines (TNF-α, IL-12, IL-18; (r ≥ 0.35, p ≤ 0.04) , chemokines (CXCL8, CCL3, CCL5, CCL15, CCL20; (r ≥0.43, p ≤ 0.01) . Notably, IL-23 is negatively correlated with adiponectin (r=-0.44, p < 0.03) in the individuals with high LDL-c. However, such association of IL-23 with inflammatory markers was not found in the individuals with low LDL-c. In conclusion, adipose tissue IL-23 may be a biomarker for inflammation progression in the individuals with high LDL-c and could be used as a therapeutic target for the treatment of metabolic syndrome. Disclosure R.Ahmad: None. S.P.Kochumon: None. A.Hasan: None. S.T.Sindhu: None. H.Arefanian: None. F.Alrashed: None. F.Almulla: None. Funding Kuwait Foundation for Advancement of Sciences (RA-2010-003)