title: Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance.
abstract: OBJECTIVE
  The role of IL-6 in the development of obesity and hepatic insulin resistance is unclear and still the subject of controversy. We aimed to determine whether global deletion of Il6 in mice (Il6 (-/-)) results in standard chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis, inflammation and insulin resistance.
  
  
  METHODS
  Male, 8-week-old Il6 (-/-) and littermate control mice were fed a standard chow or HFD for 12 weeks and phenotyped accordingly.
  
  
  RESULTS
  Il6 (-/-) mice displayed obesity, hepatosteatosis, liver inflammation and insulin resistance when compared with control mice on a standard chow diet. When fed a HFD, the Il6 (-/-) and control mice had marked, equivalent gains in body weight, fat mass and ectopic lipid deposition in the liver relative to chow-fed animals. Despite this normalisation, the greater liver inflammation, damage and insulin resistance observed in chow-fed Il6 (-/-) mice relative to control persisted when both were fed the HFD. Microarray analysis from livers of mice fed a HFD revealed that genes associated with oxidative phosphorylation, the electron transport chain and tricarboxylic acid cycle were uniformly decreased in Il6 (-/-) relative to control mice. This coincided with reduced maximal activity of the mitochondrial enzyme β-hydroxyacyl-CoA-dehydrogenase and decreased levels of mitochondrial respiratory chain proteins.
  
  
  CONCLUSIONS
  Our data suggest that IL-6 deficiency exacerbates HFD-induced hepatic insulin resistance and inflammation, a process that appears to be related to defects in mitochondrial metabolism.
authors.affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, 3008, VIC, Australia.
authors.forename: V B
authors.initials: VB
authors.lastname: Matthews
authors.forename: T L
authors.initials: TL
authors.lastname: Allen
authors.forename: S
authors.initials: S
authors.lastname: Risis
authors.forename: M H S
authors.initials: MH
authors.lastname: Chan
authors.forename: D C
authors.initials: DC
authors.lastname: Henstridge
authors.forename: N
authors.initials: N
authors.lastname: Watson
authors.forename: L A
authors.initials: LA
authors.lastname: Zaffino
authors.forename: J R
authors.initials: JR
authors.lastname: Babb
authors.forename: J
authors.initials: J
authors.lastname: Boon
authors.forename: P J
authors.initials: PJ
authors.lastname: Meikle
authors.forename: J B
authors.initials: JB
authors.lastname: Jowett
authors.forename: M J
authors.initials: MJ
authors.lastname: Watt
authors.forename: J-O
authors.initials: JO
authors.lastname: Jansson
authors.forename: C R
authors.initials: CR
authors.lastname: Bruce
authors.forename: M A
authors.initials: MA
authors.lastname: Febbraio
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000235:genetics; D000818:Animals; D001823:Body Composition / Q000235:genetics; D002153:Calorimetry, Indirect; D048429:Cell Size; D004075:Diglycerides / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004075:Diglycerides; D015850:Interleukin-6; D014280:Triglycerides