title: Adipose Tissue Insulin Action and IL-6 Signaling after Exercise in Obese Mice.
abstract: BACKGROUND
  Adipose tissue insulin action is impaired in obesity and is associated with inflammation, macrophage infiltration, and polarization toward a proinflammatory phenotype. Acute exercise can reduce markers of adipose inflammation, including interleukin (IL) 6, in parallel with improvements in insulin action; however, others have provided evidence that IL-6 has anti-inflammatory properties.
  
  
  OBJECTIVE
  This study aimed to examine the relation between IL-6 signaling, macrophage infiltration, and polarization and insulin action in inguinal fat after acute exercise in obese, insulin-resistant mice.
  
  
  METHODS
  Male C57BL/6 mice were fed a low-fat diet (10% kcal lard) or a high-fat diet (HFD, 60% kcal lard) for 7 wk and then underwent an acute bout of exercise (2-h treadmill running: 15 m·min, 5% incline).
  
  
  RESULTS
  The HFD resulted in increased body mass, glucose intolerance, and attenuated insulin-induced AKT Thr308 phosphorylation in inguinal fat. This was accompanied by increases in indices of macrophage infiltration (F4/80, CD68, and monocyte chemoattractant protein-1 expression) and polarization toward an M1 phenotype (increased expression of CD11c, CD11c/galactose-type C-type lectin 1, and inducible nitric oxide synthase). Immunofluorescence imaging demonstrated increased F4/80- and CD11c-positive cells with the HFD. Two hours after exercise, the insulin-induced activation of AKT Th308 phosphorylation was recovered in HFD mice. This was accompanied by an upregulation of IL-6 and IL-10 signaling, as demonstrated by increased expression of IL-6, IL-10, and SOCS3 as well as STAT3 phosphorylation. Furthermore, acute exercise resulted in a shift toward reduction in M1 polarization indicated by a decrease in the ratio of CD11c to galactose-type C-type lectin 1 mRNA as well as a decline in F4/80- and CD11c-positive cells.
  
  
  CONCLUSIONS
  The results suggest a link between exercise-induced increases in IL-6, reductions in indices of M1 macrophages, and increased IL-10, a reputed anti-inflammatory cytokine with insulin-sensitizing properties.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, CANADA.
authors.forename: Rebecca E K
authors.initials: RE
authors.lastname: Macpherson
authors.forename: Jason S
authors.initials: JS
authors.lastname: Huber
authors.forename: Scott
authors.initials: S
authors.lastname: Frendo-Cumbo
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Simpson
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015992:Body Mass Index; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012420:Running / Q000502:physiology
chemical_list: D007328:Insulin; D015850:Interleukin-6; D016753:Interleukin-10