Cited by 60Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Increased adipose tissue expression of IL-18R and its ligand IL-18 associates with inflammation and insulin resistance in obesity

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Ahmad, Rasheed, Thomas, Reeby, Kochumon, Shihab, Sindhu, Sardar·2017·Immunity Inflammation and Disease

Abstract

INTRODUCTION: The proinflammatory cytokine IL-18 is involved in the pathogenesis of metabolic syndrome. While the changes in IL-18 are known, IL-18R expression and relationship with IL-18 and other inflammatory markers in the adipose tissue in obesity/type-2 diabetes (T2D) remain unclear. METHODS: We, therefore, determined the adipose tissue expression of IL-18R and IL-18 mRNA/protein in lean, overweight, and obese individuals with and without T2D, 15 each, using qRT-PCR, immunohistochemistry, and confocal microscopy. Data (mean ± SEM) were analyzed using unpaired t-test and Pearson's correlation (r); all P values ≤0.05 were considered statistically significant. RESULTS: We found the upregulated gene/protein expression of IL-18R and IL-18 in non-diabetic obese/overweight as compared with lean individuals (P < 0.05). BMI correlated positively (P < 0.05) with the adipose tissue expression of IL-18R (mRNA: r = 0.90 protein: r = 0.84) and IL-18 (mRNA: r = 0.84 protein: r = 0.80). Similarly, in T2D individuals, gene and protein expression of IL-18R/IL-18 was significantly higher in obese as compared with overweight/lean individuals. The BMI was associated with the changes in both IL-18R (mRNA: r = 0.55 protein: r = 0.50) and IL-18 (mRNA: r = 0.53 protein: r = 0.57) expression. IL-18R/IL-18 gene expression in the adipose tissue was positively associated (P < 0.05) with local gene expression of other inflammatory markers including CD11c, CD86, CD68, CD163, TNF-α, and CCL5. Homeostatic model assessment of insulin resistance (HOMA-IR) was higher in diabetic/non-diabetic obese and it correlated with BMI (P < 0.05). IL-18R and IL-18 mRNA/protein expression in obesity was associated with HOMA-IR only in non-diabetics. CONCLUSIONS: The adipose tissue IL-18R/IL-18 expression is enhanced in obesity which associates with proinflammatory gene signature and insulin resistance in these individuals.

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  1. [18]Dinarello, C. A. 2007 Interleukin‐18 and the pathogenesis of inflammatory diseases. Semin. Nephrol. 27(1): 98– 114. 17336692

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Authors
Ahmad, R., Thomas, R., Kochumon, S., & Sindhu, S.
Affiliations
Dasman Diabetes Institute (KW)
Corresponding author
  • Ahmad, Rasheed
  • Sindhu, Sardar
Venue
Immunity Inflammation and Disease
Publisher
Wiley
Published
2017-05-15
Volume
5
Issue
3
Pages
318-335
ISSN
2050-4527 (ISSN-L)
OpenAlex
W2616359831
Cited by
60
References
43
Citations by year
2026: 2 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 2 · 2020: 11 · 2019: 5 · 2018: 7
FWCI
4.93
Type
journal article
Language
en
Open access
Locations
  • Immunity Inflammation and Disease (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Kuwait Foundation for the Advancement of Sciences (RC‐14016001)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
IL-18 receptor, adipose tissue, obesity, type 2 diabetes, insulin resistance, inflammation, metabolic syndrome, body mass index, inflammatory markers, TNF-α, RANTES, CD11c, CD68, CD163, CD86, HOMA-IR, gene expression, cytokines, adipocytes
MeSH terms
Adipose Tissue, Aged, Female, Gene Expression Regulation, Humans, Inflammation, Insulin Resistance, Male, Middle Aged, Obesity, Interleukin-18, Receptors, Interleukin-18

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