Two weeks of intermittent hypoxic exposure induce lipolysis at the fat tissue level in healthy human subjects

Introduction: Associated cardiovascular morbidity in Obstructive Sleep Apnea Syndrome is mainly caused by chronic intermittent hypoxia (CIH) stimulus originating sympathetic hyperactivity. In rodent exposed to CIH, the adipose tissue is the host of local inflammation and metabolism alterations. Our objective was to assess the impact of increased sympathetic activity induced by 14 nights of CIH exposure on Glucose control, lipid profile and subcutaneous fat tissue in non-obese healthy humans. Methods: In this prospective, single-blinded cross-over study, 12 subjects underwent 2 phases of exposure of 14 nights randomized to CIH vs.air. Sympathetic activity was measured by peroneal microneurography. Fasting glucose, insulin, c-peptide and FFA were assessed at rest and during a multisampling oral glucose tolerance test. Subcutaneous adipose tissue biopsies were obtained after each phase of exposure. We assessed morphological and functional changes of the adipose tissue using immuno-histology and RT-PCR. Results: After two weeks exposures of CIH versus room air, sympathetic activity significantly increased (p<0.05). Although insulin sensitivity seemed not to change significantly, fasting FFA increased. At the fat tissue level, IH induced shrunken adipocytes (3.3 vs. 2.7 x10³μm²; p = 0.03), increased lipolysis (Hormon Sensitive Lipase expression x 2.95; p = 0.02) and increased lipogenesis (Fatty Acid Synthase expression x 3.62; p = 0.04). Conclusion: In this experimental setting of high sympathetic tone, CIH induced an increase in lipolysis that may be partly responsible for associated cardio metabolic consequences.