{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:05:00Z","timestamp":1779512700816,"version":"3.53.1"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFC3605600"],"award-info":[{"award-number":["2023YFC3605600"]}]},{"name":"Shanghai Top Priority Research Center Program","award":["2023ZZ02009"],"award-info":[{"award-number":["2023ZZ02009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic intermittent hypoxia (CIH), the cardinal pathophysiological feature of obstructive sleep apnea, is increasingly recognized as an important modifier of metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanisms remain incompletely understood. In this study, male C57BL\/6 mice were fed a standard diet or a high-fat diet (HFD) and exposed to normoxia or CIH for 8 weeks. Histological, ultrastructural, biochemical, transcriptomic, proteomic, and metabolomic analyses were integrated to characterize hepatic alterations induced by CIH under metabolic stress. CIH markedly aggravated HFD-induced liver injury, as evidenced by increased body fat, hepatomegaly, serum transaminases, steatosis, mitochondrial ultrastructural alterations, and inflammatory infiltration. Mechanistically, CIH promoted hepatic lipid metabolic reprogramming by suppressing the PPAR\u03b1\/CPT1A fatty acid \u03b2-oxidation axis while enhancing the SREBP-1c\/FASN\/PLIN2 lipogenic pathway, impaired the Nrf2\/HO-1\/SLC7A11\/GPX4 antioxidant defense system, increased lipid peroxidation and iron accumulation, and activated NF-\u03baB\/NLRP3 signaling. These findings support a multifactorial model in which CIH functions as an additional hypoxic stressor that exacerbates HFD-induced MASLD-like liver injury through coordinated metabolic, oxidative, and inflammatory dysregulation.<\/jats:p>","DOI":"10.3390\/biom16050751","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Intermittent Hypoxia Exacerbates High-Fat Diet-Induced MASLD Through Lipid Metabolic Reprogramming, Impaired Antioxidant Defense, and NF-\u03baB\/NLRP3 Activation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4270-0180","authenticated-orcid":false,"given":"Lisong","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihang","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujie","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichan","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-537X","authenticated-orcid":false,"given":"Jun","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3033-8873","authenticated-orcid":false,"given":"Yuehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S2213-8587(24)00318-8","article-title":"Metabolic dysfunction-associated steatotic liver disease: Heterogeneous pathomechanisms and effectiveness of metabolism-based treatment","volume":"13","author":"Stefan","year":"2025","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"156015","DOI":"10.1016\/j.metabol.2024.156015","article-title":"Diagnostics and omics technologies for the detection and prediction of metabolic dysfunction-associated steatotic liver disease-related malignancies","volume":"161","author":"Lan","year":"2024","journal-title":"Metabolism"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Romeo, M., Silvestrin, A., Senese, G., Di Nardo, F., Napolitano, C., Vaia, P., Coppola, A., Federico, P., Dallio, M., and Federico, A. 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