Visceral white fat remodeling contributes to intermittent hypoxia-induced atherogenesis

Objective: Obstructive sleep apnea is a highly prevalent disease characterized by repetitive upper airway collapse during sleep leading to intermittent hypoxia. Cardio-metabolic complications of sleep apnea have been mostly attributed to intermittent hypoxia. These consequences could be mediated through intermittent hypoxia-related alterations of the visceral white fat, as it is recognized for playing an important role in inflammation, atherogenesis and insulin resistance. Methods: Epididymal adipose tissue alterations were investigated in twenty-week-old non obese male apolipoprotein E-deficient mice exposed to intermittent hypoxia (21-5% FiO2, 60s cycle, 8h/day) or air for 6 weeks. These adipose tissue alterations, as well as metabolic alterations and aortic atherosclerosis, were then assessed in lipectomized or sham-operated mice exposed to IH or air for 6 weeks. Results: Intermittent hypoxia induced morphological (shrunken adipocytes), functional (increased UCP-1 expression) and inflammatory (increased macrophage recruitment and secretion of IL-6 and TNF-) remodeling of epididymal adipose tissue. Hypoxic mice presented more severe dyslipidemia and atherosclerosis lesions, and developed insulin resistance. Epididymal lipectomy attenuated both intermittent hypoxia-induced dyslipidemia and atherogenesis, but did not improve insulin sensitivity. Conclusion: Our results confirmed that the dyslipidemic and proatherogenic effects of intermittent hypoxia are partly mediated through morphological, functional and inflammatory remodeling of visceral white fat, regardless of any obesity.