title: Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance.
abstract: OBJECTIVE
  Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known.
  
  
  METHODS
  We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed.
  
  
  RESULTS
  The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic-euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1).
  
  
  CONCLUSIONS
  These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St West, Hamilton, ON, Canada L8N 3Z5.
authors.forename: R
authors.initials: R
authors.lastname: Palanivel
authors.forename: M D
authors.initials: MD
authors.lastname: Fullerton
authors.forename: S
authors.initials: S
authors.lastname: Galic
authors.forename: J
authors.initials: J
authors.lastname: Honeyman
authors.forename: K A
authors.initials: KA
authors.lastname: Hewitt
authors.forename: S B
authors.initials: SB
authors.lastname: Jorgensen
authors.forename: G R
authors.initials: GR
authors.lastname: Steinberg
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D018149:Glucose Intolerance / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D012737:Sex Factors; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins