Duivenvoorde Loes P M, van Schothorst Evert M, Derous Davina, van der Stelt Inge, Masania Jinit, Rabbani Naila, Thornalley Paul J, Keijer Jaap
Human and Animal Physiology, Wageningen University, De Elst 1, 6708 WD, Wageningen, The Netherlands.
Pflugers Arch. 2015 Jun;467(6):1179-93. doi: 10.1007/s00424-014-1553-8. Epub 2014 Jul 1.
Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-invasive challenge test that measures the flexibility to adapt metabolism. Metabolic inflexibility is one of the hallmarks of the metabolic syndrome. To test whether OxR can be used to reveal early diet-induced health effects, we exposed mice to a low-fat (LF) or high-fat (HF) diet for only 5 days. The response to OxR was assessed by calorimetric measurements, followed by analysis of gene expression in liver and epididymal white adipose tissue (eWAT) and serum markers for e.g. protein glycation and oxidation. Although HF feeding increased body weight, HF and LF mice did not differ in indirect calorimetric values under normoxic conditions and in a fasting state. Exposure to OxR; however, increased oxygen consumption and lipid oxidation in HF mice versus LF mice. Furthermore, OxR induced gluconeogenesis and an antioxidant response in the liver of HF mice, whereas it induced de novo lipogenesis and an antioxidant response in eWAT of LF mice, indicating that HF and LF mice differed in their adaptation to OxR. OxR also increased serum markers of protein glycation and oxidation in HF mice, whereas these changes were absent in LF mice. Cumulatively, OxR is a promising new method to test food products on potential beneficial effects for human health.
激发试验会使体内稳态受到压力，可能会揭示在未受刺激条件下仍被掩盖的健康偏差。理想情况下，激发试验是非侵入性的，并且适用于动物实验的早期阶段。氧限制（OxR；基于环境轻度常压缺氧）是一种非侵入性激发试验，用于测量代谢适应的灵活性。代谢灵活性受损是代谢综合征的标志之一。为了测试OxR是否可用于揭示早期饮食诱导的健康影响，我们仅将小鼠暴露于低脂（LF）或高脂（HF）饮食5天。通过量热测量评估对OxR的反应，随后分析肝脏和附睾白色脂肪组织（eWAT）中的基因表达以及例如蛋白质糖基化和氧化的血清标志物。尽管高脂喂养增加了体重，但在常氧条件下和禁食状态下，高脂和低脂小鼠的间接量热值并无差异。然而，与低脂小鼠相比，暴露于OxR会增加高脂小鼠的耗氧量和脂质氧化。此外，OxR在高脂小鼠肝脏中诱导糖异生和抗氧化反应，而在低脂小鼠的eWAT中诱导从头脂肪生成和抗氧化反应，这表明高脂和低脂小鼠在对OxR的适应方面存在差异。OxR还增加了高脂小鼠中蛋白质糖基化和氧化的血清标志物，而低脂小鼠中则没有这些变化。总的来说，OxR是一种很有前景的新方法，可用于测试食品对人类健康的潜在有益影响。
