Obstructive sleep apnea (OSA) affects 1 billion people worldwide. Its main feature is chronic intermittent hypoxia (IH), responsible for metabolic and cardiovascular (CV) diseases. Type 2 diabetes is highly prevalent in OSA patients and is also recognized to be an independent CV risk factor. The multi-pathologic status of OSA patients partially explains why the gold standard treatment of OSA fails to decrease CV events. Here, we aim at suggest new strategies against OSA-associated comorbidities, based on studies demonstrating that IH induces oxidative stress and metabolic alterations. Photobiomodulation (PBM) is a non-invasive method recently shown to improve insulin resistance in obese mice and alter oxidative stress.

We hypothesize that PBM improves insulin resistance induced by IH by preserving insulin signaling pathways and reducing oxidative stress in insulin-sensitive organs.

Male C57BL/6J mice were randomized in 4 groups, submitted to either IH (14 days (D), 21–5% FiO₂, 60s cycle, 8h/day) or normoxia (N), and treated or not with PBM every day (630nm, 5J/cm², 120s). At D11, insulin sensitivity was assessed by insulin tolerance test (0.5 IU/kg, ip). At the end of exposure, liver, skeletal muscle, white adipose tissue (WAT) and heart were harvested to explore canonical insulin signaling pathway by western-blot and, oxidative stress was assessed by enzymatic activity and O₂.- content measurements.

IH induces systemic insulin resistance and impairs insulin signaling in liver and WAT, characterized by a decrease in ser473P-Akt/Akt ratio, that was not observed in skeletal muscle and heart. This is associated with an increase in O₂.- content in liver and skeletal muscle without any change in enzymatic activities. PBM significantly and specifically improves systemic insulin sensitivity in IH group. Also, PBM prevents the decrease in ser473P-Akt/Akt ratio induced by IH in WAT and decreases O₂.- content in liver.

Depending on the organ, IH alters canonical insulin signaling pathway (WAT and liver) and induces oxidative stress (liver and skeletal muscle); potentially explaining why IH impairs systemic insulin sensitivity. Interestingly, PBM significantly improves systemic insulin sensitivity in IH condition and this could be explained by an abolition of IH-induced insulin signaling pathway alteration in WAT, and oxidative stress in liver. Thus, by increasing insulin sensitivity, PBM could improve metabolic and subsequent CV outcomes in apneic patients.