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Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children
BACKGROUND: Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating ad...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658151/ https://www.ncbi.nlm.nih.gov/pubmed/29073286 http://dx.doi.org/10.1371/journal.pone.0187068 |
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author | Keustermans, Genoveva van der Heijden, Laila B. Boer, Berlinda Scholman, Rianne Nuboer, Roos Pasterkamp, Gerard Prakken, Berent de Jager, Wilco Kalkhoven, Eric Janse, Arieke J. Schipper, Henk S. |
author_facet | Keustermans, Genoveva van der Heijden, Laila B. Boer, Berlinda Scholman, Rianne Nuboer, Roos Pasterkamp, Gerard Prakken, Berent de Jager, Wilco Kalkhoven, Eric Janse, Arieke J. Schipper, Henk S. |
author_sort | Keustermans, Genoveva |
collection | PubMed |
description | BACKGROUND: Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far. Here, we aim to establish the expression of adiponectin and leptin receptors on circulating immune cells in obese children pre and post-lifestyle intervention compared to normal weight control children. METHODS: 13 obese children before and after a 1-year lifestyle intervention were compared with an age and sex-matched normal weight control group of 15 children. Next to routine clinical and biochemical parameters, circulating adipokines were measured, and flow cytometric analysis of adiponectin receptor 1 and 2 (AdipoR1, AdipoR2) and leptin receptor expression on peripheral blood mononuclear cell subsets was performed. RESULTS: Obese children exhibited typical clinical and biochemical characteristics compared to controls, including a higher BMI-SD, blood pressure and circulating leptin levels, combined with a lower insulin sensitivity index (QUICKI). The 1-year lifestyle intervention resulted in stabilization of their BMI-SD. Overall, circulating leukocyte subsets showed distinct adipokine receptor expression profiles. While monocytes expressed high levels of all adipokine receptors, NK and iNKT cells predominantly expressed AdipoR2, and B-lymphocytes and CD4(+) and CD8(+) T-lymphocyte subsets expressed AdipoR2 as well as leptin receptor. Strikingly though, leukocyte subset numbers and adipokine receptor expression profiles were largely similar in obese children and controls. Obese children showed higher naïve B-cell numbers, and pre-intervention also higher numbers of immature transition B-cells and intermediate CD14(++)CD16(+) monocytes combined with lower total monocyte numbers, compared to controls. Furthermore, adiponectin receptor 1 expression on nonclassical CD14(+)CD16(++) monocytes was consistently upregulated in obese children pre-intervention, compared to controls. However, none of the differences in leukocyte subset numbers and adipokine receptor expression profiles between obese children and controls remained significant after multiple testing correction. CONCLUSIONS: First, the distinct adipokine receptor profiles of circulating leukocyte subsets may partly explain the differential impact of adipokines on leukocyte subsets. Second, the similarities in adipokine receptor expression profiles between obese children and normal weight controls suggest that adipokine signaling in childhood obesity is primarily modulated by circulating adipokine levels, instead of adipokine receptor expression. |
format | Online Article Text |
id | pubmed-5658151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56581512017-11-09 Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children Keustermans, Genoveva van der Heijden, Laila B. Boer, Berlinda Scholman, Rianne Nuboer, Roos Pasterkamp, Gerard Prakken, Berent de Jager, Wilco Kalkhoven, Eric Janse, Arieke J. Schipper, Henk S. PLoS One Research Article BACKGROUND: Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far. Here, we aim to establish the expression of adiponectin and leptin receptors on circulating immune cells in obese children pre and post-lifestyle intervention compared to normal weight control children. METHODS: 13 obese children before and after a 1-year lifestyle intervention were compared with an age and sex-matched normal weight control group of 15 children. Next to routine clinical and biochemical parameters, circulating adipokines were measured, and flow cytometric analysis of adiponectin receptor 1 and 2 (AdipoR1, AdipoR2) and leptin receptor expression on peripheral blood mononuclear cell subsets was performed. RESULTS: Obese children exhibited typical clinical and biochemical characteristics compared to controls, including a higher BMI-SD, blood pressure and circulating leptin levels, combined with a lower insulin sensitivity index (QUICKI). The 1-year lifestyle intervention resulted in stabilization of their BMI-SD. Overall, circulating leukocyte subsets showed distinct adipokine receptor expression profiles. While monocytes expressed high levels of all adipokine receptors, NK and iNKT cells predominantly expressed AdipoR2, and B-lymphocytes and CD4(+) and CD8(+) T-lymphocyte subsets expressed AdipoR2 as well as leptin receptor. Strikingly though, leukocyte subset numbers and adipokine receptor expression profiles were largely similar in obese children and controls. Obese children showed higher naïve B-cell numbers, and pre-intervention also higher numbers of immature transition B-cells and intermediate CD14(++)CD16(+) monocytes combined with lower total monocyte numbers, compared to controls. Furthermore, adiponectin receptor 1 expression on nonclassical CD14(+)CD16(++) monocytes was consistently upregulated in obese children pre-intervention, compared to controls. However, none of the differences in leukocyte subset numbers and adipokine receptor expression profiles between obese children and controls remained significant after multiple testing correction. CONCLUSIONS: First, the distinct adipokine receptor profiles of circulating leukocyte subsets may partly explain the differential impact of adipokines on leukocyte subsets. Second, the similarities in adipokine receptor expression profiles between obese children and normal weight controls suggest that adipokine signaling in childhood obesity is primarily modulated by circulating adipokine levels, instead of adipokine receptor expression. Public Library of Science 2017-10-26 /pmc/articles/PMC5658151/ /pubmed/29073286 http://dx.doi.org/10.1371/journal.pone.0187068 Text en © 2017 Keustermans et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Keustermans, Genoveva van der Heijden, Laila B. Boer, Berlinda Scholman, Rianne Nuboer, Roos Pasterkamp, Gerard Prakken, Berent de Jager, Wilco Kalkhoven, Eric Janse, Arieke J. Schipper, Henk S. Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children |
title | Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children |
title_full | Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children |
title_fullStr | Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children |
title_full_unstemmed | Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children |
title_short | Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children |
title_sort | differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658151/ https://www.ncbi.nlm.nih.gov/pubmed/29073286 http://dx.doi.org/10.1371/journal.pone.0187068 |
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