RT info:eu-repo/semantics/article
T1 Chronic intermittent hypoxia-induced dysmetabolism is associated with hepatic oxidative stress, mitochondrial dysfunction and inflammation
A1 Fernandes, Joana L.
A1 Martins, Fátima O.
A1 Olea Fraile, Elena
A1 Prieto Lloret, Jesús
A1 Braga, Patrícia C.
A1 Sacramento, Joana F.
A1 Sequeira, Catarina O.
A1 Negrinho, Ana P.
A1 Pereira, Sofia A.
A1 Alves, Marco G.
A1 Rocher Martín, María Asunción
A1 Conde, Silvia V.
K1 Sleep disorders
K1 Obstructive sleep apnean
K1 Chronic intermittent hypoxia
K1 Insulin resistance
K1 Metabolic disorders
K1 Mitochondrial dysfunction
K1 Inflammation
K1 32 Ciencias Médicas
K1 2411.08 Metabolismo Humano
K1 2415 Biología Molecular
K1 2302 Bioquímica
AB 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.
PB MDPI
SN 2076-3921
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/67885
UL https://uvadoc.uva.es/handle/10324/67885
LA eng
NO Antioxidants, 2023, Vol. 12, Nº. 11, 1910
NO Producción Científica
DS UVaDOC
RD 23-nov-2024