{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:56:54Z","timestamp":1793692614598,"version":"4.5.1"},"reference-count":38,"publisher":"European Respiratory Society (ERS)","issue":"4","funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007772","name":"Agir pour les Maladies Chroniques","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2016,12,20]]},"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>\n                    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\n                    <jats:italic>in vitro<\/jats:italic>\n                    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.\n                  <\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1183\/13993003.01731-2016","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T15:37:23Z","timestamp":1493134643000},"page":"1601731","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":186,"title":["Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation"],"prefix":"10.1183","volume":"49","author":[{"given":"Aoife 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