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A high sympathetic tone elicits increases in plasma free fatty acid and insulin. Our objective was to assess the impact of 14 nights of chronic intermittent hypoxia exposure on sympathetic activity, glucose control, lipid profile and subcutaneous fat tissue remodelling in non\u2010obese healthy humans. In this prospective, double\u2010blinded crossover study, 12 healthy subjects were randomized, among them only nine underwent the two phases of exposures of 14 nights chronic intermittent hypoxia versus air. Sympathetic activity was measured by peroneal microneurography (muscle sympathetic nerve activity) before and after each exposure. Fasting glucose, insulin, C\u2010peptide and free fatty acid were assessed at rest and during a multisampling oral glucose tolerance test. We assessed histological remodelling, adrenergic receptors, lipolysis and lipogenesis genes expression and functional changes of the adipose tissue. Two weeks of exposure of chronic intermittent hypoxia versus ambient air significantly increased sympathetic activity (<jats:italic>p<\/jats:italic>\u2009=\u20090.04). Muscle sympathetic nerve activity increased from 24.5 [18.9; 26.8] before to 21.7 [13.8; 25.7] after ambient air exposure, and from 20.6 [17.4; 23.9] before to 28.0 [24.4; 31.5] bursts per min after exposure to chronic intermittent hypoxia. After chronic intermittent hypoxia, post\u2010oral glucose tolerance test circulating free fatty acid area under the curve increased (<jats:italic>p<\/jats:italic>\u2009=\u20090.05) and free fatty acid sensitivity to insulin decreased (<jats:italic>p<\/jats:italic>\u2009=\u20090.028). In adipocyte tissue, intermittent hypoxia increased expression of lipolysis genes (adipocyte triglyceride lipase and hormone\u2010sensitive lipase) and lipogenesis genes (fatty acid synthase; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In this unique experimental setting in healthy humans, chronic intermittent hypoxia induced high sympathetic tone, lipolysis and decreased free fatty acid sensitivity to insulin. This might participate in the trajectory to systemic insulin resistance and diabetes for patients with obstructive sleep apnea.<\/jats:p>","DOI":"10.1111\/jsr.14243","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T23:58:50Z","timestamp":1718236730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Intermittent hypoxia increases lipid insulin resistance in healthy humans: A randomized crossover trial"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3341-300X","authenticated-orcid":false,"given":"Anne","family":"Brian\u00e7on\u2010Marjollet","sequence":"first","affiliation":[{"name":"Univ. 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Grenoble Alpes, HP2; Inserm U1300  Grenoble France"},{"name":"Laboratoire de Biologie Tissulaire et Ing\u00e9nierie th\u00e9rapeutique UMR5305  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0964-9423","authenticated-orcid":false,"given":"Claire","family":"Arnaud","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, HP2; Inserm U1300  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-172X","authenticated-orcid":false,"given":"Anne\u2010Laure","family":"Borel","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, HP2; Inserm U1300  Grenoble France"},{"name":"CHU Grenoble Alpes, Endocrinology, Diabetology, Nutrition  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Levy","sequence":"additional","affiliation":[{"name":"Univ. 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