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Short-term overfeeding may induce peripheral insulin resistance without altering subcutaneous adipose tissue macrophages in humans.

Tam CS, Viardot A, Clément K, Tordjman J, Tonks K, Greenfield JR, Campbell LV, Samocha-Bonet D, Heilbronn LK - Diabetes (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia.

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.

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.

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Related in: MedlinePlus

Immunohistochemistry staining of (A) macrophage-specific marker (HAM56), M1 marker (CD40), and M2 marker (CD206) phenotype macrophages in subcutaneous adipose tissue. Pictures are taken from paired representative slides, and positive cells are marked with a black arrow. B: Change in HAM56, CD40, CD206 positive cells from baseline in response to 28 days of overfeeding. (A high-quality digital representation of this figure is available in the online issue.)
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Figure 2: Immunohistochemistry staining of (A) macrophage-specific marker (HAM56), M1 marker (CD40), and M2 marker (CD206) phenotype macrophages in subcutaneous adipose tissue. Pictures are taken from paired representative slides, and positive cells are marked with a black arrow. B: Change in HAM56, CD40, CD206 positive cells from baseline in response to 28 days of overfeeding. (A high-quality digital representation of this figure is available in the online issue.)

Mentions: HAM56 labeled macrophages were mostly dispersed in the parenchyma and few crownlike structures were seen at baseline or 28 days after overfeeding (Fig. 2). As in a previous study (11), CD40 and CD206 were used as markers of M1 and M2 macrophages, respectively. We found a trend toward a higher M1/M2 ratio at 28 days of overfeeding (P = 0.05), although there were no statistical differences in the absolute numbers of CD40 (P = 0.36) and CD206 (P = 0.42) labeled cells (Fig. 2). There was little evidence of CD3 labeled T-cells at baseline or 28 days after overfeeding, with CD3+ cells only observed in 2/66 slides. At baseline, CD40 was related to liver fat (r = 0.4, P = 0.03) but no other markers of adiposity. There were no other associations between macrophage markers and adiposity or insulin resistance at baseline or in response to overfeeding (data not shown).


Short-term overfeeding may induce peripheral insulin resistance without altering subcutaneous adipose tissue macrophages in humans.

Tam CS, Viardot A, Clément K, Tordjman J, Tonks K, Greenfield JR, Campbell LV, Samocha-Bonet D, Heilbronn LK - Diabetes (2010)

Immunohistochemistry staining of (A) macrophage-specific marker (HAM56), M1 marker (CD40), and M2 marker (CD206) phenotype macrophages in subcutaneous adipose tissue. Pictures are taken from paired representative slides, and positive cells are marked with a black arrow. B: Change in HAM56, CD40, CD206 positive cells from baseline in response to 28 days of overfeeding. (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927938&req=5

Figure 2: Immunohistochemistry staining of (A) macrophage-specific marker (HAM56), M1 marker (CD40), and M2 marker (CD206) phenotype macrophages in subcutaneous adipose tissue. Pictures are taken from paired representative slides, and positive cells are marked with a black arrow. B: Change in HAM56, CD40, CD206 positive cells from baseline in response to 28 days of overfeeding. (A high-quality digital representation of this figure is available in the online issue.)
Mentions: HAM56 labeled macrophages were mostly dispersed in the parenchyma and few crownlike structures were seen at baseline or 28 days after overfeeding (Fig. 2). As in a previous study (11), CD40 and CD206 were used as markers of M1 and M2 macrophages, respectively. We found a trend toward a higher M1/M2 ratio at 28 days of overfeeding (P = 0.05), although there were no statistical differences in the absolute numbers of CD40 (P = 0.36) and CD206 (P = 0.42) labeled cells (Fig. 2). There was little evidence of CD3 labeled T-cells at baseline or 28 days after overfeeding, with CD3+ cells only observed in 2/66 slides. At baseline, CD40 was related to liver fat (r = 0.4, P = 0.03) but no other markers of adiposity. There were no other associations between macrophage markers and adiposity or insulin resistance at baseline or in response to overfeeding (data not shown).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia.

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.

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.

Show MeSH
Related in: MedlinePlus