title: Short-term overfeeding may induce peripheral insulin resistance without altering subcutaneous adipose tissue macrophages in humans.
abstract: OBJECTIVE
  Chronic low-grade inflammation is a feature of obesity and is postulated to be causal in the development of insulin resistance and type 2 diabetes. The aim of this study was to assess whether overfeeding induces peripheral insulin resistance in lean and overweight humans, and, if so, whether it is associated with increased systemic and adipose tissue inflammation.
  
  
  METHODS
  Thirty-six healthy individuals undertook 28 days of overfeeding by +1,250 kcal/day (45% fat). Weight, body composition, insulin sensitivity (hyperinsulinemic-euglycemic clamp), serum and gene expression of inflammation markers, immune cell activation, fat cell size, macrophage and T-cell numbers in abdominal subcutaneous adipose tissue (flow cytometry and immunohistochemistry) were assessed at baseline and after 28 days.
  
  
  RESULTS
  Subjects gained 2.7 +/- 1.6 kg (P < 0.001) and increased fat mass by 1.1 +/- 1.6% (P < 0.001). Insulin sensitivity decreased by 11% from 54.6 +/- 18.7 to 48.9 +/- 15.7 micromol/(kg of FFM)/min (P = 0.01). There was a significant increase in circulating C-reactive protein (P = 0.002) and monocyte chemoattractant protein-1 (P = 0.01), but no change in interleukin-6 and intercellular adhesion molecule-1. There were no changes in fat cell size, the number of adipose tissue macrophages or T-cells, or inflammatory gene expression and no change in circulating immune cell number or expression of their surface activation markers after overfeeding.
  
  
  CONCLUSIONS
  Weight gain-induced insulin resistance was observed in the absence of a significant inflammatory state, suggesting that inflammation in subcutaneous adipose tissue occurs subsequent to peripheral insulin resistance in humans.
authors.affiliation: Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia.
authors.forename: Charmaine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Alexander
authors.initials: A
authors.lastname: Viardot
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.forename: Katherine
authors.initials: K
authors.lastname: Tonks
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Greenfield
authors.forename: Lesley V
authors.initials: LV
authors.lastname: Campbell
authors.forename: Dorit
authors.initials: D
authors.lastname: Samocha-Bonet
authors.forename: Leonie K
authors.initials: LK
authors.lastname: Heilbronn
mesh_terms: D050153:Abdominal Fat / Q000166:cytology; D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000166:cytology; D015703:Antigens, CD / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D048429:Cell Size; D008076:Cholesterol, HDL / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology; D002149:Energy Intake; D005247:Feeding Behavior; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D050151:Subcutaneous Fat / Q000166:cytology / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
chemical_list: D015703:Antigens, CD; D001786:Blood Glucose; D008076:Cholesterol, HDL; D015850:Interleukin-6; D014280:Triglycerides; D018799:Intercellular Adhesion Molecule-1; D012313:RNA; D002097:C-Reactive Protein