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Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation
Obstructive sleep apnea (OSA) is a prevalent condition and strongly associated with metabolic disorders. Sleep fragmentation (SF) is a major consequence of OSA, but its contribution to OSA-related morbidities is not known. We hypothesized that SF causes specific perturbations in transcriptional netw...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357342/ https://www.ncbi.nlm.nih.gov/pubmed/22629440 http://dx.doi.org/10.1371/journal.pone.0037669 |
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author | Gharib, Sina A. Khalyfa, Abdelnaby Abdelkarim, Amal Bhushan, Bharat Gozal, David |
author_facet | Gharib, Sina A. Khalyfa, Abdelnaby Abdelkarim, Amal Bhushan, Bharat Gozal, David |
author_sort | Gharib, Sina A. |
collection | PubMed |
description | Obstructive sleep apnea (OSA) is a prevalent condition and strongly associated with metabolic disorders. Sleep fragmentation (SF) is a major consequence of OSA, but its contribution to OSA-related morbidities is not known. We hypothesized that SF causes specific perturbations in transcriptional networks of visceral fat cells, leading to systemic metabolic disturbances. We simultaneously profiled visceral adipose tissue mRNA and miRNA expression in mice exposed to 6 hours of SF during sleep, and developed a new computational framework based on gene set enrichment and network analyses to merge these data. This approach leverages known gene product interactions and biologic pathways to interrogate large-scale gene expression profiling data. We found that SF induced the activation of several distinct pathways, including those involved in insulin regulation and diabetes. Our integrative methodology identified putative controllers and regulators of the metabolic response during SF. We functionally validated our findings by demonstrating altered glucose and lipid homeostasis in sleep-fragmented mice. This is the first study to link sleep fragmentation with widespread disruptions in visceral adipose tissue transcriptome, and presents a generalizable approach to integrate mRNA-miRNA information for systematic mapping of regulatory networks. |
format | Online Article Text |
id | pubmed-3357342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33573422012-05-24 Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation Gharib, Sina A. Khalyfa, Abdelnaby Abdelkarim, Amal Bhushan, Bharat Gozal, David PLoS One Research Article Obstructive sleep apnea (OSA) is a prevalent condition and strongly associated with metabolic disorders. Sleep fragmentation (SF) is a major consequence of OSA, but its contribution to OSA-related morbidities is not known. We hypothesized that SF causes specific perturbations in transcriptional networks of visceral fat cells, leading to systemic metabolic disturbances. We simultaneously profiled visceral adipose tissue mRNA and miRNA expression in mice exposed to 6 hours of SF during sleep, and developed a new computational framework based on gene set enrichment and network analyses to merge these data. This approach leverages known gene product interactions and biologic pathways to interrogate large-scale gene expression profiling data. We found that SF induced the activation of several distinct pathways, including those involved in insulin regulation and diabetes. Our integrative methodology identified putative controllers and regulators of the metabolic response during SF. We functionally validated our findings by demonstrating altered glucose and lipid homeostasis in sleep-fragmented mice. This is the first study to link sleep fragmentation with widespread disruptions in visceral adipose tissue transcriptome, and presents a generalizable approach to integrate mRNA-miRNA information for systematic mapping of regulatory networks. Public Library of Science 2012-05-21 /pmc/articles/PMC3357342/ /pubmed/22629440 http://dx.doi.org/10.1371/journal.pone.0037669 Text en Gharib 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gharib, Sina A. Khalyfa, Abdelnaby Abdelkarim, Amal Bhushan, Bharat Gozal, David Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation |
title | Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation |
title_full | Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation |
title_fullStr | Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation |
title_full_unstemmed | Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation |
title_short | Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation |
title_sort | integrative mirna-mrna profiling of adipose tissue unravels transcriptional circuits induced by sleep fragmentation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357342/ https://www.ncbi.nlm.nih.gov/pubmed/22629440 http://dx.doi.org/10.1371/journal.pone.0037669 |
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