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

Aoife Murphy, Amandine Thomas, Sophie Crinion, Brian Kent, Murtaza Tambuwala, Aurelie Fabre, Jean-Louis PEPIN, Helen Roche, Claire ARNAUD, Silke Ryan

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalEuropean Respiratory Journal
Volume49
Early online date19 Apr 2017
DOIs
Publication statusE-pub ahead of print - 19 Apr 2017

Bibliographical note

Compliant in UIR but the embargo length was set at 14 months and did not lift within one month of the published date. Uploaded information from Unpaywall as proof of open access.

Keywords

  • obstructive sleep apnea
  • intermittent hypoxia
  • insulin resistance
  • adipose
  • tissue inflammation

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