Screening for Inflammatory Markers Identifies IL-18Rα as a Potential Link between Exenatide and Its Anti-Inflammatory Effect: New Results from the Combat-JUDO Randomized Controlled Trial

Introduction: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, metabolic associated fatty liver disease, and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to...

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Veröffentlicht in:Annals of nutrition and metabolism 2024-01, Vol.79 (6), p.522-527
Hauptverfasser: Stenlid, Rasmus, Cerenius, Sara Y., Manell, Hannes, Küçükemre Aydin, Banu, Mörwald, Katharina, Gomahr, Julian, Höghammar Mitkas, Marina, Eriksson, Ida, Ciba, Iris, Geiersberger, Sabine, Thivel, David, Weghuber, Daniel, Bergsten, Peter, Forslund, Anders
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Sprache:eng
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Zusammenfassung:Introduction: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, metabolic associated fatty liver disease, and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to treat obesity, with known anti-inflammatory properties. How the GLP-1RA exenatide effects inflammation in adolescents with obesity is not fully investigated. Methods: Forty-four patients were randomized to receive weekly subcutaneous injections with either 2 mg exenatide or placebo for 6 months. Plasma samples were collected at baseline and at the end of the study, and 92 inflammatory proteins were measured. Results: Following treatment with exenatide, 15 out of the 92 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL-18Rα was significantly lowered following treatment. Conclusions: Weekly injections with 2 mg of exenatide lowers circulating IL-18Rα in adolescents with obesity, which may be a potential link between exenatide and its anti-inflammatory effect in vivo. This contributes to exenatide’s pharmaceutical potential as a treatment for obesity beyond weight control and glucose tolerance, and should be further studied mechanistically.
ISSN:0250-6807
1421-9697
DOI:10.1159/000534725