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

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 th...

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Autores principales: Jacobsen, Mette J., Mentzel, Caroline M. Junker, Olesen, Ann Sofie, Huby, Thierry, Jørgensen, Claus B., Barrès, Romain, Fredholm, Merete, Simar, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698937/
https://www.ncbi.nlm.nih.gov/pubmed/26798656
http://dx.doi.org/10.1155/2016/8539057
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author Jacobsen, Mette J.
Mentzel, Caroline M. Junker
Olesen, Ann Sofie
Huby, Thierry
Jørgensen, Claus B.
Barrès, Romain
Fredholm, Merete
Simar, David
author_facet Jacobsen, Mette J.
Mentzel, Caroline M. Junker
Olesen, Ann Sofie
Huby, Thierry
Jørgensen, Claus B.
Barrès, Romain
Fredholm, Merete
Simar, David
author_sort Jacobsen, Mette J.
collection PubMed
description 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.
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spelling pubmed-46989372016-01-21 Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity Jacobsen, Mette J. Mentzel, Caroline M. Junker Olesen, Ann Sofie Huby, Thierry Jørgensen, Claus B. Barrès, Romain Fredholm, Merete Simar, David J Diabetes Res Research Article 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. Hindawi Publishing Corporation 2016 2015-12-21 /pmc/articles/PMC4698937/ /pubmed/26798656 http://dx.doi.org/10.1155/2016/8539057 Text en Copyright © 2016 Mette J. Jacobsen et al. https://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Research Article
Jacobsen, Mette J.
Mentzel, Caroline M. Junker
Olesen, Ann Sofie
Huby, Thierry
Jørgensen, Claus B.
Barrès, Romain
Fredholm, Merete
Simar, David
Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity
title Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity
title_full Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity
title_fullStr Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity
title_full_unstemmed Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity
title_short Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity
title_sort altered methylation profile of lymphocytes is concordant with perturbation of lipids metabolism and inflammatory response in obesity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698937/
https://www.ncbi.nlm.nih.gov/pubmed/26798656
http://dx.doi.org/10.1155/2016/8539057
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