Sleep apnea affects nearly one billion people worldwide and causes repeated episodes of oxygen deprivation during the night, known as intermittent hypoxia. A study conducted by scientists from the University of Grenoble Alpes, Inserm, and Grenoble Alpes University Hospital, published today in the journal Science Advances , shows that these episodes reorganize the liver’s biological clock, altering the daily rhythms of its metabolic activity. These findings shed light on a previously unknown aspect of the disease and could help to better target the optimal time for administering treatments to improve their effectiveness.
While the pathological consequences of intermittent hypoxia in sleep apnea are well documented, their impact on the body’s biological rhythms, governed by the circadian clock, remains largely unexplored.
In this study, scientists used a mouse model of chronic intermittent hypoxia to analyze the effects of this respiratory stress on the body over the entire day-night cycle. Focusing on the liver, the central organ of energy regulation, they combined transcriptomic, metabolomic, and physiological approaches to track adaptations in hepatic metabolic activity over time.
The results show that intermittent hypoxia not only alters certain major energy pathways orchestrated by the liver, such as glucose and lipid metabolism, but also profoundly reprograms their circadian organization. For example, metabolomic analysis reveals that nearly half of hepatic metabolites exhibit a 24-hour rhythm and that more than a third of them acquire a new rhythm under intermittent hypoxia. This redistribution of metabolic rhythms throughout the day reflects a genuine temporal reprogramming of hepatic activity and highlights a previously underestimated dimension of sleep apnea.
This research opens up new perspectives in chronomedicine. By reprogramming the liver’s metabolic rhythms, intermittent hypoxia could alter the body’s response to certain drugs, particularly those that affect blood sugar or lipid metabolism. Their effectiveness could therefore vary depending on the time of day, with optimal times for administration differing from those observed in people without this respiratory disorder. This highlights the importance of incorporating the temporal dimension into the management of sleep apnea.
Chronic intermittent hypoxia reshapes circadian metabolic architecture in a model of sleep apnea
Émilie Montellier, Guillaume Vial, Sophie Bouyon, Kousha Changizi Ashtiani, Sherif Abdelkarim, Émeline Lemarie, Antoine Boutin, Kenichiro Kinouchi, Pierre Baldi, Jean-Louis Pépin, Jonathan Gaucher
Science Advances
DOI: 10.1126/sciadv.aeb3756
