title: DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human.
abstract: 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.
  
  
  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.
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney NSW 2052, Australia. Electronic address: d.simar@unsw.edu.au.
authors.forename: David
authors.initials: D
authors.lastname: Simar
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Soetkin
authors.initials: S
authors.lastname: Versteyhe
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Donkin
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, UNSW Australia, Sydney NSW 2052, Australia.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, UNSW Australia, Sydney NSW 2052, Australia.
authors.forename: Luke
authors.initials: L
authors.lastname: Hesson
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vibe
authors.initials: V
authors.lastname: Nylander
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Fossum
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; School of Medical Sciences, UNSW Australia, Sydney NSW 2052, Australia. Electronic address: barres@sund.ku.dk.
authors.forename: Romain
authors.initials: R
authors.lastname: Barrès
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D015992:Body Mass Index; D002478:Cells, Cultured; D015331:Cohort Studies; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D007333:Insulin Resistance; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
keywords: Epigenetic changes; Flow cytometry; Leukocytes; Metabolic diseases