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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. RESEARCH DESIGN AND 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.

Type Journal
ISBN 1939-327X (Electronic) 0012-1797 (Linking)
Authors Tam, C. S.; Viardot, A.; Clement, K.; Tordjman, J.; Tonks, K.; Greenfield, J. R.; Campbell, L. V.; Samocha-Bonet, D.; Heilbronn, L. K.
Publisher Name DIABETES
Published Date 2010-10-01
Published Volume 59
Published Issue 9
Published Pages 2164-70
Status Published in-print
DOI db10-0162 [pii] 10.2337/db10-0162
URL link to publisher's version
OpenAccess link to author's accepted manuscript version