Introduction: Intermittent hypoxia (IH) as a hallmark feature of obstructive sleep apnea (OSA) is a major pathophysiological trigger for cardiovascular and metabolic diseases occurring in OSA. Obesity and OSA may interact in cardiometabolic processes and IH has been suggested to mediate its action through the visceral adipose tissue (AT) promoting a pro-inflammatory response. Metabolically dysfunctional AT in obesity is characterized by macrophage infiltration and polarization of macrophages towards a pro-inflammatory insulin resistance promoting M1, “classically activated” over an anti M2, “alternatively activated” phenotype. Aim of the study was to investigate the impact of IH on AT M1/M2 relationship in lean and diet-induced obese (DIO) mice. Methods: Male C57Bl/6 mice (5-weeks old) were fed on a low-fat diet (LF, 10%fat, n=20) or on a high-fat diet (HF, 60% fat, n=26) for 14 weeks and then randomized to 6 weeks of IH (inspired oxygen 5-21%, 60 sec cycle, 8hrs/day) or intermittent normoxia (N). Insulin tolerance test (ITT) was performed at the end of the protocol. M1 and M2 populations of the stromal vascular fraction of epididymal AT were assessed by flow cytometry.Results: As expected, HF-IH mice were significantly lighter than HF-N at the end of the study, but there was no difference in weight between LF-IH and LF-N. IH contributed to insulin resistance in both, LF and HF and this was associated with higher percentage of AT M1 macrophages (LF: N vs IH: 1.5±0.4% vs 4.3±3.7; p=0.049; HF: 6.8±2.8 vs 11.8±3.8; p=0.009). HF mice demonstrated lower M2 than LF mice (p=0.022) but there was no difference between groups on IH and N treatment.Conclusion: IH contributes to pro-inflammatory macrophage polarization in AT and insulin resistance. Further studies will determine the intermediate mechanisms underlying these events.
|Journal||American Journal of Respiratory and Critical Care Medicine|
|Publication status||Published - 18 May 2015|
Murphy, A. M., Thomas, A., Tambuwala, M., McNicholas, W. T., Roche, H. M., Taylor, C. T., ... Ryan, S. (2015). Chronic Intermittent Hypoxia Contributes To Pro-Inflammatory Macrophage Alteration In Visceral Adipose Tissue Of Lean And Obese Mice. American Journal of Respiratory and Critical Care Medicine, B30, 2691-2691.