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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...

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Autores principales: Das, Swapan Kumar, Ma, Lijun, Sharma, Neeraj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
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.
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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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