| Autor: |
Fernandes JL; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-069 Lisboa, Portugal., Martins FO; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-069 Lisboa, Portugal., Olea E; Departamento de Enfermeria, Universidad de Valladolid, 47005 Valladolid, Spain.; Unidad de Excelencia Instituto de Biomedicina y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47005 Valladolid, Spain., Prieto-Lloret J; Unidad de Excelencia Instituto de Biomedicina y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47005 Valladolid, Spain.; Departamento de Bioquímica, Biologia Molecular y Fisiologia, Universidad de Valladolid, 47005 Valladolid, Spain., Braga PC; Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal.; ITR-Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal.; Institute of Biomedicine-iBiMED and Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal., Sacramento JF; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-069 Lisboa, Portugal., Sequeira CO; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-069 Lisboa, Portugal., Negrinho AP; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-069 Lisboa, Portugal., Pereira SA; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-069 Lisboa, Portugal., Alves MG; Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal.; ITR-Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal.; Institute of Biomedicine-iBiMED and Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal., Rocher A; Unidad de Excelencia Instituto de Biomedicina y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47005 Valladolid, Spain.; Departamento de Bioquímica, Biologia Molecular y Fisiologia, Universidad de Valladolid, 47005 Valladolid, Spain., Conde SV; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-069 Lisboa, Portugal. |
| Abstrakt: |
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% O 2 ) 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. |
