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Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation

Murphy, Aoife, Thomas, Amandine, Crinion, Sophie, Kent, Brian, Tambuwala, Murtaza, Fabre, Aurelie, PEPIN, Jean-Louis, Roche, Helen, ARNAUD, Claire and Ryan, Silke (2017) Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation. European Respiratory Journal, 49 . [Journal article]

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URL: http://ow.ly/k1TX3091YBM

DOI: 10.1183/13993003.01731-2016

Abstract

Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role.We tested this hypothesis employing a comprehensive translational approach using a murine IH model of lean and diet-induced obese mice, an innovative IH system for cell cultures and a tightly controlled patient cohort.IH led to the development of insulin resistance in mice, corrected for the degree of obesity, and reduced insulin-mediated glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin-signalling pathway and downregulation of insulin-receptor substrate-1 mRNA. Providing mechanistic insight, IH induced a pro-inflammatory phenotype of visceral adipose tissue in mice with pro-inflammatory M1 macrophage polarisation correlating with the severity of insulin resistance. Complimentary in vitro analysis demonstrated that IH led to M1 polarisation of THP1-derived macrophages. In subjects without comorbidities (n=186), OSA was independently associated with insulin resistance. Furthermore, we found an independent correlation of OSA severity with the M1 macrophage inflammatory marker sCD163.This study provides evidence that IH induces a pro-inflammatory phenotype of the adipose tissue,which may be a crucial link between OSA and the development of insulin resistance.

Item Type:Journal article
Keywords:obstructive sleep apnea, intermittent hypoxia, insulin resistance, adipose tissue inflammation
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:37085
Deposited By: Dr Murtaza Tambuwala
Deposited On:06 Mar 2017 09:08
Last Modified:05 Sep 2017 12:39

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