Short-term overfeeding may induce peripheral insulin resistance without altering subcutaneous adipose tissue macrophages in humans.
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.
Tam
Charmaine S
CS
Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia.
Viardot
Alexander
A
Clément
Karine
K
Tordjman
Joan
J
Tonks
Katherine
K
Greenfield
Jerry R
JR
Campbell
Lesley V
LV
Samocha-Bonet
Dorit
D
Heilbronn
Leonie K
LK
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
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