PT  - JOURNAL ARTICLE
AU  - Aoife M. Murphy
AU  - Amandine Thomas
AU  - Sophie J. Crinion
AU  - Brian D. Kent
AU  - Murtaza M. Tambuwala
AU  - Aurelie Fabre
AU  - Jean-Louis Pepin
AU  - Helen M. Roche
AU  - Claire Arnaud
AU  - Silke Ryan
TI  - Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation
AID  - 10.1183/13993003.01731-2016
DP  - 2017 Apr 01
TA  - European Respiratory Journal
PG  - 1601731
VI  - 49
IP  - 4
4099  - http://erj.ersjournals.com/content/49/4/1601731.short
4100  - http://erj.ersjournals.com/content/49/4/1601731.full
SO  - Eur Respir J2017 Apr 01; 49
AB  - 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.Intermittent hypoxia induces inflammatory phenotype of adipose tissue leading to insulin resistance in sleep apnoea http://ow.ly/k1TX3091YBM