DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human

TY - JOUR

T1 - DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human

AU - Simar, David

AU - Versteyhe, Soetkin

AU - Donkin, Ida

AU - Liu, Jia

AU - Hesson, Luke

AU - Nylander, Vibe Charlotte

AU - Fossum, Anna

AU - Barrès, Romain

PY - 2014/9

Y1 - 2014/9

N2 - Objective Obesity is associated with low-grade inflammation and the infiltration of immune cells in insulin-sensitive tissues, leading to metabolic impairment. Epigenetic mechanisms control immune cell lineage determination, function and migration and are implicated in obesity and type 2 diabetes (T2D). The aim of this study was to determine the global DNA methylation profile of immune cells in obese and T2D individuals in a cell type-specific manner. Material and methods Fourteen obese subjects and 11 age-matched lean subjects, as well as 12 T2D obese subjects and 7 age-matched lean subjects were recruited. Global DNA methylation levels were measured in a cell type-specific manner by flow cytometry. We validated the assay against mass spectrometry measures of the total 5-methylcytosine content in cultured cells treated with the hypomethylation agent decitabine (r = 0.97, p < 0.001). Results Global DNA methylation in peripheral blood mononuclear cells, monocytes, lymphocytes or T cells was not altered in obese or T2D subjects. However, analysis of blood fractions from lean, obese, and T2D subjects showed increased methylation levels in B cells from obese and T2D subjects and in natural killer cells from T2D patients. In these cell types, DNA methylation levels were positively correlated with insulin resistance, suggesting an association between DNA methylation changes, immune function and metabolic dysfunction. Conclusions Both obesity and T2D are associated with an altered epigenetic signature of the immune system in a cell type-specific manner. These changes could contribute to the altered immune functions associated with obesity and insulin resistance.

AB - Objective Obesity is associated with low-grade inflammation and the infiltration of immune cells in insulin-sensitive tissues, leading to metabolic impairment. Epigenetic mechanisms control immune cell lineage determination, function and migration and are implicated in obesity and type 2 diabetes (T2D). The aim of this study was to determine the global DNA methylation profile of immune cells in obese and T2D individuals in a cell type-specific manner. Material and methods Fourteen obese subjects and 11 age-matched lean subjects, as well as 12 T2D obese subjects and 7 age-matched lean subjects were recruited. Global DNA methylation levels were measured in a cell type-specific manner by flow cytometry. We validated the assay against mass spectrometry measures of the total 5-methylcytosine content in cultured cells treated with the hypomethylation agent decitabine (r = 0.97, p < 0.001). Results Global DNA methylation in peripheral blood mononuclear cells, monocytes, lymphocytes or T cells was not altered in obese or T2D subjects. However, analysis of blood fractions from lean, obese, and T2D subjects showed increased methylation levels in B cells from obese and T2D subjects and in natural killer cells from T2D patients. In these cell types, DNA methylation levels were positively correlated with insulin resistance, suggesting an association between DNA methylation changes, immune function and metabolic dysfunction. Conclusions Both obesity and T2D are associated with an altered epigenetic signature of the immune system in a cell type-specific manner. These changes could contribute to the altered immune functions associated with obesity and insulin resistance.

U2 - 10.1016/j.metabol.2014.05.014

DO - 10.1016/j.metabol.2014.05.014

M3 - Journal article

C2 - 24996265

SN - 0026-0495

VL - 63

JO - Metabolism

JF - Metabolism

IS - 9

ER -