2026-04-27T22:00:56Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/678852026-04-07T06:53:11Zcom_10324_1149com_10324_931com_10324_894col_10324_1274

Fernandes, Joana L. Martins, Fatima O. Olea Fraile, Elena Prieto Lloret, Jesús Braga, Patrícia C. Sacramento, Joana F. Sequeira, Catarina O. Negrinho, Ana P. Pereira, Sofia A. Alves, Marco G. Rocher Martín, María Asunción Conde, Silvia V. 2024-05-29T08:05:41Z 2024-05-29T08:05:41Z 2023 Antioxidants, 2023, Vol. 12, Nº. 11, 1910 2076-3921 https://uvadoc.uva.es/handle/10324/67885 10.3390/antiox12111910 1910 11 Antioxidants 12 2076-3921 Producción Científica The association between obstructive sleep apnea (OSA) and metabolic disorders is well-established; however, the underlying mechanisms that elucidate this relationship remain incompletely understood. Since the liver is a major organ in the maintenance of metabolic homeostasis, we hypothesize that liver dysfunction plays a crucial role in the pathogenesis of metabolic dysfunction associated with obstructive sleep apnea (OSA). Herein, we explored the underlying mechanisms of this association within the liver. Experiments were performed in male Wistar rats fed with a control or high fat (HF) diet (60% lipid-rich) for 12 weeks. Half of the groups were exposed to chronic intermittent hypoxia (CIH) (30 hypoxic (5% O2) cycles, 8 h/day) that mimics OSA, in the last 15 days. Insulin sensitivity and glucose tolerance were assessed. Liver samples were collected for evaluation of lipid deposition, insulin signaling, glucose homeostasis, hypoxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation. Both the CIH and HF diet induced dysmetabolism, a state not aggravated in animals submitted to HF plus CIH. CIH aggravates hepatic lipid deposition in obese animals. Hypoxia-inducible factors levels were altered by these stimuli. CIH decreased the levels of oxidative phosphorylation complexes in both groups and the levels of SOD-1. The HF diet reduced mitochondrial density and hepatic antioxidant capacity. The CIH and HF diet produced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that hepatic mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA. Junta de Castilla y León y Sociedad Portugal de Diabetes (Grupo de Investigaión Fundamental e Translacional) - (grant CCVC8485) Fundación Portuguesa para la Ciencia y la Tecnología (FCT) - (CEECIND/04266/2017, CEEC IND/02428/2018 y 2021.03439.CEECIND) Fundación Portuguesa para la Ciencia y la Tecnología (FCT) - (projects UIDB/04050/2020 and UIDB/04033/2020) Laboratorio de Investigación Integrativa y Traslacional en Salud de la Población (ITR) (LA/P/0064/2020) - (project UI/BD/150750/2020) application/pdf eng MDPI info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ © 2023 The authors Atribución 4.0 Internacional Sleep disorders Obstructive sleep apnean Chronic intermittent hypoxia Insulin resistance Metabolic disorders Mitochondrial dysfunction Inflammation 32 Ciencias Médicas 2411.08 Metabolismo Humano 2415 Biología Molecular 2302 Bioquímica Chronic intermittent hypoxia-induced dysmetabolism is associated with hepatic oxidative stress, mitochondrial dysfunction and inflammation info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.mdpi.com/2076-3921/12/11/1910 SI