Metabolic Dysfunction in Obstrutive Sleep Apnea: is there a Role for the Liver?

• Autor(a) principal: Fernandes, Joana Leandro
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/160291
• topic: Obstructive sleep apnea; metabolic disorders; mitochondrial dysfunction; inflammation; oxidative stress; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

The link between obstructive sleep apnea (OSA) and metabolic disorders is unquestio-nable. Despite different mechanisms have been proposed to explain this relationship, namely the sympathetic nervous system overactivation, alterations in adipokine levels, oxidative stress in white adipose tissue, none is consensual and do not completely clarify this relationship. The liver is a major organ in the maintenance of metabolic homeostasis and whose dysfunction is involved in several diseases, including metabolic diseases. Hence, we hypothesize that liver dysfunction is key in the development of metabolic dysfunction commonly associated with obstructive sleep apnea (OSA). Moreover, we aimed to explore the underlying mechanisms of this association within the liver. Male Wistar Rats were divided into two groups: a control and an obese group fed with 60% lipid-enriched diet (HF diet) for 12 weeks. Half of the animals from each group were sub-mitted to a severe chronic intermittent hypoxia (CIH) paradigm (40s, 5%O2/80s air, 8h/day), that mimics OSA, in the last 14 days. Liver samples were then collected and used for the eval-uation of different parameters: lipid deposition, insulin signalling, glucose homeostasis, hy-poxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation, using western blot, histological and fluorescent immunohistochemistry, HPLC and enzymatic assays. Both CIH and HF diet led to insulin resistance and glucose intolerance, effects not aggra-vated 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 oxi-dative phosphorylation complexes in both groups and the levels of superoxide dismutase 1. HF diet reduced mitochondrial density and hepatic antioxidant capacity. CIH and HF diet pro-duced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA.