Cardio-metabolic complications of obstructive sleep apnea: Impact of chronic intermittent hypoxia on cardiac insulin signaling

Background Chronic intermittent hypoxia (IH) is the major feature of obstructive sleep apnea syndrome (OSA), well known to induce cardiac remodeling and contractile dysfunction as well as systemic insulin resistance. Currently, no studies have investigated the impact of IH on cardiac insulin signaling. Thus, we aimed to highlight the effects of chronic IH in both lean and obese mice on: – cardiac insulin signaling; – cardiac function and remodeling. Methods C57BL/6 J male mice were fed either low-fat (LF) or high-fat (HF) diet for 20 weeks, and exposed to IH (21–5% FiO2, 60 s cycle, 8 h/day) or normoxia (N) for the last 6 weeks. Systemic insulin sensitivity was evaluated by an insulin tolerance test (ITT). Cardiac remodeling and contractile function were assessed by echocardiography. Ultimately, hearts were withdrawn for biochemical analysis of the main effectors of the insulin signaling. Results In LF mice, IH induced systemic insulin resistance and altered cardiac insulin signaling (insulin-induced PAkt: 1,05 vs. 3,01 fold increase vs. NaCl in IH and N respectively, P P Conclusion We highlighted a novel role for IH in the development of cardiac insulin resistance, which was associated with a blunted cardiac response to β-adrenergic stimulation. Further studies are now needed to better understand the relationship between these two mechanisms.