Increased Adipose Tissue Expression of IL-23 Associates with Inflammatory Markers in People with High LDL Cholesterol

Cells. 2022 Sep 29;11(19):3072. doi: 10.3390/cells11193072.

Abstract

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.

Keywords: IL-23; LDL-cholesterol; adipose tissue; cytokines/chemokines; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / metabolism
  • Adipose Tissue / metabolism
  • Biomarkers / metabolism
  • Chemokines / metabolism
  • Cholesterol / metabolism
  • Cholesterol, HDL
  • Cholesterol, LDL / metabolism
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • Humans
  • Hyperlipidemias* / metabolism
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-23 / metabolism
  • Interleukin-23 Subunit p19 / metabolism*
  • Metabolic Syndrome* / metabolism
  • Toll-Like Receptor 8 / metabolism
  • Triglycerides / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adiponectin
  • Biomarkers
  • Chemokines
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cytokines
  • IL23A protein, human
  • Inflammation Mediators
  • Interleukin-18
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Toll-Like Receptor 8
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Cholesterol

Grants and funding

This study was supported by funds from the Kuwait Foundation for Advancement of Sciences (Grant #: RA 2010–003; RA AM 2016-007).