Increased Adipose Tissue Expression of IL-23 Associates with Inflammatory Markers in People with High LDL Cholesterol.
Shihab KochumonAmal HasanFatema Al-RashedSardar SindhuReeby ThomasTexy JacobAmnah Al-SayyarHossein ArefanianAshraf Al MadhounEbaa Al-OzairiFawaz AlzaidHeikki A KoistinenFahd Al-MullaJaakko TuomilehtoRasheed AhmadPublished in: Cells (2022)
Chronic low-grade inflammation induced by obesity is a central risk factor for the development of metabolic syndrome. High low-density lipoprotein cholesterol (LDL-c) induces inflammation, which is a common denominator in metabolic syndrome. IL-23 plays a significant role in the pathogenesis of meta-inflammatory diseases; however, its relationship with LDL-c remains elusive. In this cross-sectional study, we determined whether the adipose tissue IL-23 expression was associated with other inflammatory mediators in people with increased plasma LDL-c concentrations. Subcutaneous adipose tissue biopsies were collected from 60 people, sub-divided into two groups based on their plasma LDL-c concentrations (<2.9 and ≥2.9 mmol/L). Adipose expression of IL-23 and inflammatory markers were determined using real-time qRT-PCR; plasma concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and LDL-c were determined using the standard method; and adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Adipose IL-23 transcripts were found to be increased in people with high LDL-c, compared to low LDL-c group (H-LDL-c: 1.63 ± 0.10-Fold; L-LDL-c: 1.27 ± 0.09-Fold; p < 0.01); IL-23 correlated positively with LDL-c (r = 0.471, p < 0.0001). Immunochemistry analysis showed that AT IL-23 protein expression was also elevated in the people with H-LDL-c. IL-23 expression in the high LDL-c group was associated with multiple adipose inflammatory biomarkers ( p ≤ 0.05), including macrophage markers (CD11c, CD68, CD86, CD127), TLRs (TLR8, TLR10), IRF3, pro-inflammatory cytokines (TNF-α, IL-12, IL-18), and chemokines (CXCL8, CCL3, CCL5, CCL15, CCL20). Notably, in this cohort, IL-23 expression correlated inversely with plasma adiponectin. In conclusion, adipose IL-23 may be an inflammatory biomarker for disease progression in people with high LDL-c.
Keyphrases
- adipose tissue
- low density lipoprotein
- metabolic syndrome
- insulin resistance
- poor prognosis
- oxidative stress
- low grade
- high fat diet
- binding protein
- type diabetes
- toll like receptor
- cardiovascular disease
- rheumatoid arthritis
- liver injury
- immune response
- long non coding rna
- liver fibrosis
- physical activity
- high grade
- drug induced