Increased adipose tissue expression of IL-18R and its ligand IL-18 associates with inflammation and insulin resistance in obesity
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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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In adipose tissue, IL-18 is released by both macrophages and adipocytes in obese mice and humans.
“In the adipose tissue, the latest cytokine is released by both macrophages and adipocytes in obese mice and humans [237,238].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [237]
IL-18 expression seems to be tightly correlated with other proinflammatory markers such as TNFα.
“IL-18 expression seems to be tightly correlated to other proinflammatory markers, such as TNFα, and a linear correlation between IL-18 and BMI was found in humans [237].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [237]
A linear correlation between IL-18 and BMI was found in humans.
“IL-18 expression seems to be tightly correlated to other proinflammatory markers, such as TNFα, and a linear correlation between IL-18 and BMI was found in humans [237].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [237]
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The Role of IL-18 and Human Cytomegalovirus in Type 1 Diabetes Mellitus in Thi-Qar Province
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Mora‐Godínez, S., Marín‐Obispo, L. M., Mellado-Negrete, A., de la Garza, A. L., Tamez‐Rivera, O., Navarro-Guerra, M., Telles-Ramirez, B., Martínez-Ledesma, E., Castaño‐Moreno, E., Senés‐Guerrero, C., et al. (2026) · Computational and Structural Biotechnology Journal · doi:10.34133/csbj.0194
- 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)
- PMC
- PMC5569378
- 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
- gold
- doi.org
- Licence
- 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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