In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats.
In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats.
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DOI：
10.1183/09031936.98.12030658
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发表时间：
1998-09
期刊：
影响因子：
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通讯作者：
C. Pison;C. Chauvin;H. Perrault;C. Schwebel;J. Lafond;C. Boujet;X. Leverve
中科院分区：
文献类型：
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作者：
C. Pison;C. Chauvin;H. Perrault;C. Schwebel;J. Lafond;C. Boujet;X. Leverve
众所周知，缺氧会通过影响肝功能从而影响葡萄糖稳态来影响碳水化合物代谢。本研究的目的是检查碳水化合物、脂质和蛋白质对 48 小时缺氧的代谢反应，以及使用常氧对照和禁食状态下的缺氧动物的激素适应，以标准化因缺氧反应而观察到的明显吞咽不足。缺氧暴露（吸入氧分数 (FI,O2) = 0.1）导致更大的体重减轻（对照组为 -23 +/- 3.6% 对比 -16 +/- 2%，p<0.001）。缺氧加上禁食导致血浆葡萄糖、乳酸、胰岛素和儿茶酚胺浓度显着增加，而游离脂肪酸和β-羟基丁酸的增加被消除。血浆氨基酸模式的变化不受缺氧的影响。在缺氧组中，肝糖原消耗明显不那么明显，而磷酸烯醇丙酮酸羧激酶（肝脏糖异生的关键酶）活性和转录增强则因缺氧而消失。总体而言，禁食 48 小时的大鼠缺氧暴露导致了一种独特的模式，该模式不同于对损伤或禁食本身的反应。从基因表达到减肥，氧气似乎在禁食的代谢适应中发挥着核心作用。由于与禁食相关的低氧血症对营养平衡具有不利影响，因此目前的观察结果可能在慢性呼吸道疾病低氧血症急性加重的情况下具有临床相关性。
Hypoxia is well known to affect carbohydrate metabolism through its action on liver function and thus on glucose homeostasis. The aim of this study was to examine the carbohydrate, lipid and protein metabolic responses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to standardize for the marked hypophagia observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2% in controls, p<0.001). Hypoxia plus fasting led to a significant increase in plasma glucose, lactate, insulin and catecholamine concentrations, while the increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptation to fasting, from gene expression to weight loss. Since hypoxaemia associated with fasting has detrimental effects on nutritional balance, the present observations may be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.