Metabolic dysfunction in OSA: Is there something new under the sun?

The growing number of patients with obstructive sleep apnea is challenging healthcaresystems worldwide. Obstructive sleep apnea is characterized by chronic intermittenthypoxaemia, episodes of apnea and hypopnea, and fragmented sleep. Cardiovascularand metabolic diseases are common in obstructive sleep apnea, also in lean patients.Further, comorbidity burden is not unambiguously linked to the severity of obstructivesleep apnea. There is a growing body of evidence revealing diverse functions beyondthe conventional tasks of different organs such as carotid body and gut microbiota.Chronic intermittent hypoxia and sleep loss due to sleep fragmentation are associatedwith insulin resistance. Indeed, carotid body is a multi-sensor organ not sensoringonly hypoxia and hypercapnia but also acting as a metabolic sensor. The emergingevidence shows that obstructive sleep apnea and particularly chronic intermittenthypoxia is associated with non-alcoholic fatty liver disease. Gut dysbiosis seems to bean important factor in the pathophysiology of obstructive sleep apnea and its conse-quences. The impact of sleep fragmentation and intermittent hypoxia on the develop-ment of metabolic syndrome may be mediated via altered gut microbiota. Circadianmisalignment seems to have an impact on the cardiometabolic risk in obstructivesleep apnea. Dysfunction of cerebral metabolism is also related to hypoxia and sleepfragmentation. Therefore, obstructive sleep apnea may alter cerebral metabolism andpredispose to neurocognitive impairment. Moreover, recent data show that obstruc-tive sleep apnea independently predicts impaired lipid levels. This mini-review willprovide novel insights into the mechanisms of metabolic dysfunction in obstructivesleep apnea combining recent evidence from basic, translational and clinical research,and discuss the impact of positive airway pressure treatment on metabolic disorders.