Dept. of Internal Medicine, Division of Pulmonary Diseases, Univ. Hospital Giessen and Marburg GmbH, 35043 Marburg, Germany.
J Appl Physiol (1985). 2011 Sep;111(3):881-90. doi: 10.1152/japplphysiol.00492.2011. Epub 2011 Jul 7.
Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both obesity and OSA are associated with insulin resistance and systemic inflammation, which may be attributable to tissue hypoxia. We hypothesized that a pattern of hypoxic exposure determines both oxygen profiles in peripheral tissues and systemic metabolic outcomes, and that obesity has a modifying effect. Lean and obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60) [inspired O₂ fraction (Fi(O₂)) 21-5%, 60/h], IH 12 times/h (Fi(O₂) 5% for 15 s, 12/h), sustained hypoxia (SH; Fi(O₂) 10%), or normoxia while fasting. Tissue oxygen partial pressure (Pti(O₂)) in liver, skeletal muscle and epididymal fat, plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis factor-α (TNF-α) were measured. In lean mice, IH60 caused oxygen swings in the liver, whereas fluctuations of Pti(O₂) were attenuated in muscle and abolished in fat. In obese mice, baseline liver Pti(O₂) was lower than in lean mice, whereas muscle and fat Pti(O₂) did not differ. During IH, Pti(O₂) was similar in obese and lean mice. All hypoxic regimens caused insulin resistance. In lean mice, hypoxia significantly increased leptin, especially during SH (44-fold); IH60, but not SH, induced a 2.5- to 3-fold increase in TNF-α secretion by fat. Obesity was associated with striking increases in leptin and TNF-α, which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens.
阻塞性睡眠呼吸暂停（OSA）导致睡眠期间间歇性缺氧（IH）。肥胖和 OSA 都与胰岛素抵抗和全身炎症有关，这可能归因于组织缺氧。我们假设缺氧暴露模式决定外周组织的氧谱和全身代谢结果，而肥胖具有修饰作用。瘦鼠和肥胖鼠 C57BL6 分别接受 12 小时的间歇性缺氧 60 次/小时（IH60）[吸入 O₂分数（Fi(O₂)）21-5%，60 次/小时]、12 次/小时 IH（Fi(O₂)5%持续 15 秒，12 次/小时）、持续缺氧（SH；Fi(O₂)10%）或在禁食期间常氧。测量肝脏、骨骼肌和附睾脂肪的组织氧分压（Pti(O₂)）、血浆瘦素、脂联素、胰岛素、血糖和脂肪肿瘤坏死因子-α（TNF-α）。在瘦鼠中，IH60 导致肝脏氧波动，而肌肉和脂肪中的 Pti(O₂)波动减弱。在肥胖鼠中，基础肝脏 Pti(O₂)低于瘦鼠，而肌肉和脂肪中的 Pti(O₂)没有差异。在 IH 期间，肥胖鼠和瘦鼠的 Pti(O₂)相似。所有低氧方案均导致胰岛素抵抗。在瘦鼠中，缺氧显著增加瘦素，尤其是在 SH 期间（增加 44 倍）；IH60，但不是 SH，诱导脂肪分泌 TNF-α增加 2.5-3 倍。肥胖与瘦素和 TNF-α的显著增加有关，这超过了缺氧的影响。总之，IH60 导致肝脏和肌肉的氧波动以及脂肪的稳定缺氧。IH 和 SH 诱导胰岛素抵抗，但炎症仅在瘦鼠中由 IH60 引起增加。肥胖导致严重的炎症，急性低氧方案不会加剧这种炎症。
