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Journal of Diabetes Research
Volume 2016, Article ID 8539057, 11 pages
http://dx.doi.org/10.1155/2016/8539057
Research Article

Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity

1Animal Genetics, Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
2Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S 1166, Integrative Biology of Atherosclerosis Team, 75013 Paris, France
3Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, 75013 Paris, France
4The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
5Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia

Received 9 June 2015; Revised 31 August 2015; Accepted 6 September 2015

Academic Editor: Ed Randell

Copyright © 2016 Mette J. Jacobsen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Obesity is associated with immunological perturbations that contribute to insulin resistance. Epigenetic mechanisms can control immune functions and have been linked to metabolic complications, although their contribution to insulin resistance still remains unclear. In this study, we investigated the link between metabolic dysfunction and immune alterations with the epigenetic signature in leukocytes in a porcine model of obesity. Global DNA methylation of circulating leukocytes, adipose tissue leukocyte trafficking, and macrophage polarisation were established by flow cytometry. Adipose tissue inflammation and metabolic function were further characterised by quantification of metabolites and expression levels of genes associated with obesity and inflammation. Here we show that obese pigs showed bigger visceral fat pads, higher levels of circulating LDL cholesterol, and impaired glucose tolerance. These changes coincided with impaired metabolism, sustained macrophages infiltration, and increased inflammation in the adipose tissue. Those immune alterations were linked to global DNA hypermethylation in both B-cells and T-cells. Our results provide novel insight into the possible contribution of immune cell epigenetics into the immunological disturbances observed in obesity. The dramatic changes in the transcriptomic and epigenetic signature of circulating lymphocytes reinforce the concept that epigenetic processes participate in the increased immune cell activation and impaired metabolic functions in obesity.