Photobiomodulation Alleviates Insulin Resistance Induced by Intermittent Hypoxia, Through Preservation of Adipose Tissue Insulin Signaling and Reduction of Hepatic Oxidative Stress in Mice

ABSTRACT Aim Chronic intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), contributes to metabolic diseases and enhances associated cardiovascular (CV) complications through oxidative stress and metabolic alterations. We hypothesize that photobiomodulation (PBM), a non‐invasive low‐level laser therapy, prevents IH‐induced insulin resistance (IR), by preserving insulin signalization and reducing oxidative stress in insulin‐sensitive organs. Methods Male C57BL/6J mice were randomized in 4 groups, submitted to either 2‐weeks IH (21%–5% FiO 2 , 60 s cycle, 8 h/day) or normoxia (N), with or without PBM (630 nm, 5 J/cm 2 , 32 mW, 120 s, 5 days/week). At day 11, insulin sensitivity was assessed by insulin tolerance test. Then, canonical insulin signaling pathway was explored by western‐blot, and oxidative stress was assessed by measurement of enzymatic activity, O 2 · − content, and lipid and protein oxidation in liver, gastrocnemius (GC) muscle, and epididymal white adipose tissue (eWAT). Results IH induces systemic IR, impairs insulin signaling in liver and eWAT, and increases hepatic O 2 · − content, while pro/anti‐oxidant enzyme activities were unchanged. Interestingly, in IH group only, PBM significantly improves systemic insulin sensitivity, prevents eWAT insulin signaling alteration and decreases hepatic O 2 · − content. Conclusion PBM alleviates systemic insulin resistance, restores eWAT insulin signaling, and limits hepatic oxidative stress induced by IH. By enhancing insulin sensitivity, PBM could be proposed as a new therapeutic strategy against OSA‐associated metabolic comorbidities.