title: Knock-down of IL-1Ra in obese mice decreases liver inflammation and improves insulin sensitivity.
abstract: Interleukin 1 Receptor antagonist (IL-1Ra) is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight. A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1. These results demonstrate that normalization of plasma IL-1Ra concentration improves insulin sensitivity in diet- induced obese mice.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Niclas
authors.initials: N
authors.lastname: Franck
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California, United States of America; Clinical and Experimental Endocrinology, Catholic University Leuven, Leuven, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Maris
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nalbandian
authors.affiliation: Pfizer Inc. Research Laboratories, Cambridge, Massachusetts, United States of America.
authors.forename: Saswata
authors.initials: S
authors.lastname: Talukdar
authors.affiliation: Department of Orthopedic Surgery, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Simon
authors.initials: S
authors.lastname: Schenk
authors.affiliation: Pfizer Inc. Research Laboratories, Cambridge, Massachusetts, United States of America.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hofmann
authors.affiliation: Pfizer Inc. Research Laboratories, Cambridge, Massachusetts, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Bullough
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Olivia
authors.initials: O
authors.lastname: Osborn
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D004032:Diet; D005951:Glucose Tolerance Test; D006505:Hepatitis / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics / Q000378:metabolism*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein