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Adipose tissue gene expression and metabolic health of obese adults
Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardio-metabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422777/ https://www.ncbi.nlm.nih.gov/pubmed/25520251 http://dx.doi.org/10.1038/ijo.2014.210 |
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author | Das, Swapan Kumar Ma, Lijun Sharma, Neeraj |
author_facet | Das, Swapan Kumar Ma, Lijun Sharma, Neeraj |
author_sort | Das, Swapan Kumar |
collection | PubMed |
description | Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardio-metabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes remain challenging. We conducted unsupervised hierarchical clustering analysis of subcutaneous adipose tissue transcripts from 30 obese men and women ≥40 years old. Despite similar BMIs in all subjects, we found two distinct subgroups, one metabolically healthy (Group 1) and one metabolically unhealthy (Group 2). Subjects in Group 2 showed significantly higher total cholesterol (p=0.005), LDL cholesterol (p=0.006), 2h-Insulin during OGTT (p=0.015) and lower insulin sensitivity (S(I), p=0.029) compared to Group 1. We identified significant up-regulation of 141 genes (e.g. MMP9 and SPP1) and down-regulation of 17 genes (e.g. NDRG4 and GINS3) in group 2 subjects. Intriguingly, these differentially expressed transcripts were enriched for genes involved in cardiovascular disease-related processes (p=2.81×10(−11)–3.74×10(−02)) and pathways involved in immune and inflammatory response (p=8.32×10(−5)–0.04). Two down-regulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models. Our study provides evidence that perturbations in the adipose tissue gene expression network are important in defining metabolic health in obese subjects. |
format | Online Article Text |
id | pubmed-4422777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44227772015-11-01 Adipose tissue gene expression and metabolic health of obese adults Das, Swapan Kumar Ma, Lijun Sharma, Neeraj Int J Obes (Lond) Article Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardio-metabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes remain challenging. We conducted unsupervised hierarchical clustering analysis of subcutaneous adipose tissue transcripts from 30 obese men and women ≥40 years old. Despite similar BMIs in all subjects, we found two distinct subgroups, one metabolically healthy (Group 1) and one metabolically unhealthy (Group 2). Subjects in Group 2 showed significantly higher total cholesterol (p=0.005), LDL cholesterol (p=0.006), 2h-Insulin during OGTT (p=0.015) and lower insulin sensitivity (S(I), p=0.029) compared to Group 1. We identified significant up-regulation of 141 genes (e.g. MMP9 and SPP1) and down-regulation of 17 genes (e.g. NDRG4 and GINS3) in group 2 subjects. Intriguingly, these differentially expressed transcripts were enriched for genes involved in cardiovascular disease-related processes (p=2.81×10(−11)–3.74×10(−02)) and pathways involved in immune and inflammatory response (p=8.32×10(−5)–0.04). Two down-regulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models. Our study provides evidence that perturbations in the adipose tissue gene expression network are important in defining metabolic health in obese subjects. 2014-12-18 2015-05 /pmc/articles/PMC4422777/ /pubmed/25520251 http://dx.doi.org/10.1038/ijo.2014.210 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Das, Swapan Kumar Ma, Lijun Sharma, Neeraj Adipose tissue gene expression and metabolic health of obese adults |
title | Adipose tissue gene expression and metabolic health of obese adults |
title_full | Adipose tissue gene expression and metabolic health of obese adults |
title_fullStr | Adipose tissue gene expression and metabolic health of obese adults |
title_full_unstemmed | Adipose tissue gene expression and metabolic health of obese adults |
title_short | Adipose tissue gene expression and metabolic health of obese adults |
title_sort | adipose tissue gene expression and metabolic health of obese adults |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422777/ https://www.ncbi.nlm.nih.gov/pubmed/25520251 http://dx.doi.org/10.1038/ijo.2014.210 |
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