Journal article
Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice
B Lindegaard, VB Matthews, C Brandt, P Hojman, TL Allen, E Estevez, MJ Watt, CR Bruce, OH Mortensen, S Syberg, C Rudnicka, J Abildgaard, H Pilegaard, J Hidalgo, S Ditlevsen, TJ Alsted, AN Madsen, BK Pedersen, MA Febbraio
Diabetes | AMER DIABETES ASSOC | Published : 2013
DOI: 10.2337/db12-1095
Abstract
Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high-fat diet (HFD)-induced insulin resistance by activating AMP-activated protein kinase (AMPK). We studied mice with a global deletion of the a-isoform of the IL-18 receptor (IL-18R-/-) fed a standard chow or HFD. We next performed gain-of-function experiments in skeletal muscle, in vitro, ex vivo, and in vivo. We show that IL-18 is implicated in metabolic homeostasis, inflammation, and insulin resistance via mechanisms involving the activation of AMPK in skeletal muscle. IL-18R-/- mice display increased weight gain, ectopic lipid deposition, inflammation, a..
View full abstractGrants
Awarded by European Commission
Funding Acknowledgements
This study was supported, in part, by a grant from the National Health and Medical Research Council of Australia (NHMRC grant no. 526606). This study was further supported by the Danish Council for Independent Research-Medical Sciences, the Commission of the European Communities (grant agreement no. 223576-MYOAGE), and by grants from the Novo Nordisk Foundation, Horslevfonden, the Danish National Research Foundation (#10-083807), Hojmosegardlegatet, Fonden for Laegevidenskabens Fremme, and Direktor Jacob Madsen og Hustru Olga Madsens Fond. The Centre of Inflammation and Metabolism (CIM) and The Rodent Metabolic Phenotyping Center is part of the UNIK Project: Food, Fitness & Pharma for Health and Disease (see www.foodfitnesspharma.ku.dk) supported by the Danish Ministry of Science, Technology, and Innovation. The CIM is a member of DD2-the Danish Center for Strategic Research in Type 2 Diabetes (the Danish Council for Strategic Research, grant no. 09-067009 and 09-075724). The Copenhagen Muscle Research Centre is supported by a grant from the Capital Region of Denmark. M. A. F. is a Senior Principal Research Fellow, M.J.W. is a Senior Research Fellow, and C. R. B. and V. B. M. are Career Development Fellows of the NHMRC. The CIM is supported by a grant from the Danish National Research Foundation (#02-512-55). B. L. was supported by a grant from the Danish National Research Foundation (#09-063656). B. L. received postdoctoral fellowship support from a grant from the Danish National Research Foundation.