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Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents
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Aims/hypothesis The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents.Methods We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents.Results We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn ( -/- )animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn ( -/- ) animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5 days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake.Conclusions/interpretation The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistance.
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“Minor dairy proteins and peptides, especially lactoferrin, also show anti-inflammatory effects in different models (687 -689) , and hence there is potential for a variety of milk peptides to have anti-inflammatory effects, but there are no or insufficient human studies to allow evaluation of their efficacy.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [687]
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Metadata
- Authors
- Somm, E., Cettour-Rose, P., Asensio, C., Charollais, A., Klein, M., Theander-Carrillo, C., Juge-Aubry, C. E., Dayer, J. M., Nicklin, M. J. H., Meda, P., Rohner-Jeanrenaud, F., & Meier, C. A.
- Affiliations
- University Hospital of Geneva (CH)
- University of Geneva (CH)
- Royal Hallamshire Hospital (GB)
- Corresponding author
- Meier, C. A.
- Venue
- Diabetologia
- Published
- 2005-12-30
- Volume
- 49
- Issue
- 2
- Pages
- 387-393
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2153117216
- Cited by
- 111
- References
- 35
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2022: 2 · 2021: 7 · 2020: 3 · 2018: 7 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 7 · 2012: 9
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (109402, 105889, 63443, 3200B0, 103618, 310000, 3100A0)
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK063443)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- interleukin-1 receptor antagonist, IL-1 signaling, diet-induced obesity, insulin resistance, insulin sensitivity, glucose homeostasis, white adipose tissue, muscle glucose uptake, high-fat diet, anti-inflammatory cytokines
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Dietary Fats, Gene Expression Regulation, Insulin, Insulin Resistance, Interleukin-1, Islets of Langerhans, Male, Mice, Inbred C57BL, Obesity, RNA, Messenger, Sialoglycoproteins, Glucose Clamp Technique, Signal Transduction, Up-Regulation, Gene Deletion, Receptors, Interleukin-1, Mice, Knockout, Muscle, Skeletal, Mice, Receptors, Interleukin-1 Type II, Interleukin 1 Receptor Antagonist Protein
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