title: Deficiency of haematopoietic-cell-derived IL-10 does not exacerbate high-fat-diet-induced inflammation or insulin resistance in mice.
abstract: OBJECTIVE
  Recent work has identified the important roles of M1 pro-inflammatory and M2 anti-inflammatory macrophages in the regulation of insulin sensitivity. Specifically, increased numbers of M2 macrophages and a decrease in M1 macrophages within the adipose tissue are associated with a state of enhanced insulin sensitivity. IL-10 is an anti-inflammatory cytokine and is a critical effector molecule of M2 macrophages.
  
  
  METHODS
  In the present study, we examined the contribution of haematopoietic-cell-derived IL-10 to the development of obesity-induced inflammation and insulin resistance. We hypothesised that haematopoietic-cell-restricted deletion of IL-10 would exacerbate obesity-induced inflammation and insulin resistance. Lethally irradiated wild-type recipient mice receiving bone marrow from either wild-type or Il10-knockout mice were placed on either a chow or a high-fat diet for a period of 12 weeks and assessed for alterations in body composition, tissue inflammation and glucose and insulin tolerance.
  
  
  RESULTS
  Contrary to our hypothesis, neither inflammation, as measured by the activation of pro-inflammatory stress kinases and gene expression of several pro-inflammatory cytokines in the adipose tissue and liver, nor diet-induced obesity and insulin resistance were exacerbated by the deletion of haematopoietic-cell-derived IL-10. Interestingly, however, Il10 mRNA expression and IL-10 protein production in liver and/or adipose tissue were markedly elevated in Il10-knockout bone-marrow-transplanted mice relative to wild-type bone marrow-transplanted mice.
  
  
  CONCLUSIONS
  These data show that deletion of IL-10 from the haematopoietic system does not potentiate high-fat diet-induced inflammation or insulin resistance.
authors.affiliation: Cellular & Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, 3008 VIC, Australia.
authors.forename: G M
authors.initials: GM
authors.lastname: Kowalski
authors.forename: H T
authors.initials: HT
authors.lastname: Nicholls
authors.forename: S
authors.initials: S
authors.lastname: Risis
authors.forename: N K
authors.initials: NK
authors.lastname: Watson
authors.forename: P
authors.initials: P
authors.lastname: Kanellakis
authors.forename: C R
authors.initials: CR
authors.lastname: Bruce
authors.forename: A
authors.initials: A
authors.lastname: Bobik
authors.forename: G I
authors.initials: GI
authors.lastname: Lancaster
authors.forename: M A
authors.initials: MA
authors.lastname: Febbraio
mesh_terms: D000818:Animals; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D004041:Dietary Fats / Q000009:adverse effects*; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10