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Adv."],"published-print":{"date-parts":[[2026,2,27]]},"abstract":"<jats:p>Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (IH) during sleep, is increasingly recognized as a driver of metabolic dysfunction. However, its impact on circadian metabolic regulation remains poorly understood. Here, we investigated how chronic IH reshapes 24-hour hepatic and systemic metabolic programs in a mouse model mimicking OSA-associated chronic hypoxia. Through integrated circadian transcriptomic, metabolomic, and physiological 24-hour profiling, we show that 4 weeks of rest phase\u2013restricted IH reprograms hepatic and systemic metabolism in a time-specific manner. This reorganization involves the coordinated circadian regulation of glucose, lipid, and redox pathways, with a shift away from oxidative metabolism toward oxygen-sparing processes such as gluconeogenesis, glycogen turnover, and lipid mobilization. These changes align with the hypoxic phase exposure and coincide with reshaped hepatic metabolite oscillations and systemic autonomic rhythms, supporting a functional adaptation to intermittent oxygen availability. Mechanistically, we identify the cAMP-CREB1 pathway as a driver of circadian transcriptional remodeling in the liver and a central integrator of IH-dependent adrenergic stress. Our findings establish chronic IH as a potent metabolic zeitgeber that rewires hepatic transcriptional and metabolic programs, revealing a circadian dimension to the metabolic consequences of sleep-disordered breathing.<\/jats:p>","DOI":"10.1126\/sciadv.aeb3756","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T18:59:04Z","timestamp":1772045944000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Chronic intermittent hypoxia reshapes circadian metabolic architecture in a model of sleep apnea"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5069-3536","authenticated-orcid":true,"given":"Emilie","family":"Montellier","sequence":"first","affiliation":[{"name":"Univ. Grenoble Alpes (UGA), Inserm (French National Institute of Health and Medical Research) Unit 1300, Hypoxia and Physiopathology Laboratory (HP2), Grenoble, France."},{"name":"Univ. Grenoble Alpes (UGA), Inserm (French National Institute of Health and Medical Research) Unit 1209, CNRS (French National Center for Scientific Research) Unit 5309, Institute for Advanced Biosciences (IAB), Grenoble, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-8526","authenticated-orcid":true,"given":"Guillaume","family":"Vial","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes (UGA), Inserm (French National Institute of Health and Medical Research) Unit 1300, Hypoxia and Physiopathology Laboratory (HP2), Grenoble, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7868-1884","authenticated-orcid":true,"given":"Sophie","family":"Bouyon","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes (UGA), Inserm (French National Institute of Health and Medical Research) Unit 1300, Hypoxia and Physiopathology Laboratory (HP2), Grenoble, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9233-5899","authenticated-orcid":true,"given":"Kousha Changizi","family":"Ashtiani","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA, USA."},{"name":"AI in Science Institute, University of California, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7456-6133","authenticated-orcid":true,"given":"Sherif","family":"Abdelkarim","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA, USA."},{"name":"AI in Science Institute, University of California, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3341-5665","authenticated-orcid":true,"given":"Emeline","family":"Lemarie","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes (UGA), Inserm (French National Institute of Health and Medical Research) Unit 1300, Hypoxia and Physiopathology Laboratory (HP2), Grenoble, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5269-2035","authenticated-orcid":true,"given":"Antoine","family":"Boutin","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes (UGA), Inserm (French National Institute of Health and Medical Research) Unit 1300, Hypoxia and Physiopathology Laboratory (HP2), Grenoble, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4743-2583","authenticated-orcid":true,"given":"Kenichiro","family":"Kinouchi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8752-4664","authenticated-orcid":true,"given":"Pierre","family":"Baldi","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA, USA."},{"name":"AI in Science Institute, University of California, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-2358","authenticated-orcid":true,"given":"Jean-Louis","family":"P\u00e9pin","sequence":"additional","affiliation":[{"name":"Univ. 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