title: IL-37 protects against obesity-induced inflammation and insulin resistance.
abstract: Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Dov B
authors.initials: DB
authors.lastname: Ballak
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Janna A
authors.initials: JA
authors.lastname: van Diepen
authors.affiliation: Children's Hospital, Ludwig-Maximilians University, Munich D-80337, Germany.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Moschen
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Jansen
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Hijmans
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Groenhof
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Leenders
authors.affiliation: Children's Hospital, Ludwig-Maximilians University, Munich D-80337, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Bufler
authors.affiliation: Department of Human Nutrition, Wageningen University, Wageningen 6703 HD, The Netherlands.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.affiliation: Department of Human Nutrition, Wageningen University, Wageningen 6703 HD, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Human Nutrition, Wageningen University, Wageningen 6703 HD, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Suzhao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: SooHyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Clinical Biochemistry, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Eini
authors.affiliation: Department of Clinical Biochemistry, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
authors.forename: Eli C
authors.initials: EC
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Christian Doppler Research Laboratory for Gut Inflammation, Medical University Innsbruck, Innsbruck A-6020, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Tilg
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.affiliation: 1] Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands [2] Department of Medicine, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: 1] Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands [2] Department of Human Nutrition, Wageningen University, Wageningen 6703 HD, The Netherlands.
authors.forename: Rinke
authors.initials: R
authors.lastname: Stienstra
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000009:adverse effects; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood / Q000235:genetics; D007333:Insulin Resistance; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D004041:Dietary Fats; C508587:IL37 protein, human; D007328:Insulin; D007375:Interleukin-1; D055372:AMP-Activated Protein Kinases