Extreme environmental conditions at high altitude, such as hypobaric hypoxia, low temperature, and strong UV radiation, pose a great challenge to the survival of animals. Although the mechanisms of adaptation to high-altitude environments have attracted much attention for native plateau species, the underlying metabolic regulation remains unclear. Here, we used a multi-platform metabolomic analysis to compare metabolic profiles of liver between high- and low-altitude populations of toad-headed lizards, Phrynocephalus vlangalii, from the Qinghai–Tibet Plateau. A total of 191 differential metabolites were identified, consisting of 108 up-regulated and 83 down-regulated metabolites in high-altitude lizards as compared with values for low-altitude lizards. Pathway analysis revealed that the significantly different metabolites were associated with carbohydrate metabolism, amino acid metabolism, purine metabolism, and glycerolipid metabolism. Most intermediary metabolites of glycolysis and the tricarboxylic acid cycle were not significantly altered between the two altitudes, but most free fatty acids as well as β-hydroxybutyric acid were significantly lower in the high-altitude population. This may suggest that high-altitude lizards rely more on carbohydrates as their main energy fuel rather than lipids. Higher levels of phospholipids occurred in the liver of high-altitude populations, suggesting that membrane lipids may undergo adaptive remodeling in response to low-temperature stress at high altitude. In summary, this study demonstrates that metabolic profiles differ substantially between high- and low-altitude lizard populations, and that these differential metabolites and metabolic pathways can provide new insights to reveal mechanisms of adaptation to extreme environments at high altitude.

中文翻译：

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比较代谢组学分析揭示了蟾头胎生蜥蜴（Phrynocephalus vlangalii）的高海拔适应

高海拔地区的低压缺氧、低温、强紫外线等极端环境条件，给动物的生存带来了巨大的挑战。尽管高原本土物种适应高海拔环境的机制备受关注，但其潜在的代谢调控仍不清楚。在这里，我们使用多平台代谢组学分析来比较来自青藏高原的高海拔和低海拔蟾头蜥（Phrynocephalus vlangalii）种群的肝脏代谢特征。共鉴定出 191 种差异代谢物，其中高海拔蜥蜴与低海拔蜥蜴相比，有 108 种上调代谢物和 83 种下调代谢物。通路分析显示，显着不同的代谢物与碳水化合物代谢、氨基酸代谢、嘌呤代谢和甘油脂代谢相关。大多数糖酵解和三羧酸循环的中间代谢物在两个海拔高度之间没有显着改变，但大多数游离脂肪酸以及β-羟基丁酸在高海拔人群中显着降低。这可能表明高海拔蜥蜴更多地依赖碳水化合物作为主要能量燃料，而不是脂质。高海拔人群的肝脏中磷脂水平较高，这表明膜脂可能会发生适应性重塑以应对高海拔的低温应激。总之，这项研究表明，高海拔和低海拔蜥蜴种群的代谢特征存在显着差异，这些差异代谢物和代谢途径可以为揭示高海拔极端环境的适应机制提供新的见解。