Obstructive sleep apnea and CPAP therapy alter distinct transcriptional programs in subcutaneous fat tissue.

Autor:	Gharib SA; Computational Medicine Core, Center for Lung Biology, University of Washington, Seattle, WA.; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA., Hurley AL; Mercer Health, Coldwater, OH., Rosen MJ; Department of Surgery, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH., Spilsbury JC; Department of Population & Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH., Schell AE; Department of Otolaryngology, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH.; Division of Pulmonary, Critical Care, and Sleep Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH., Mehra R; Sleep Disorders Center of the Neurologic Institute, Respiratory Institute, Heart and Vascular Institute and Lerner Research Institute, Cleveland Clinic, Cleveland, OH., Patel SR; Center for Sleep and Cardiovascular Outcomes Research, University of Pittsburgh, Pittsburgh, PA.; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.
Jazyk:	angličtina
Zdroj:	Sleep [Sleep] 2020 Jun 15; Vol. 43 (6).
DOI:	10.1093/sleep/zsz314
Abstrakt:	Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states, and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment's molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea-hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g. interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy. (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu