Beyond glucose: metabolic shifts in responses to the effects of the oral glucose tolerance test and the high-fructose diet in rats
Beyond glucose: metabolic shifts in responses to the effects of the oral glucose tolerance test and the high-fructose diet in rats
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DOI：
10.1039/c0mb00246a
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发表时间：
2011-01-01
影响因子：
--
通讯作者：
Cai, Zongwei
中科院分区：
文献类型：
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作者：
Lin, Shuhai;Yang, Zhu;Cai, Zongwei
高果糖饮食喂养的大鼠作为胰岛素抵抗模型之一，被广泛用于了解2型糖尿病的发病机制。然而，该大鼠模型的系统水平代谢谱尚未得到清晰解读。为解决这一问题，采用基于质谱的代谢组学方法来揭示健康或糖尿病大鼠口服葡萄糖耐量试验（oGTT）效应的代谢快照，并描绘高果糖饮食喂养大鼠组织中的代谢特征。几种有差异的代谢物被突出显示，以揭示健康和糖尿病大鼠中oGTT效应的代谢扰动，涉及氨基酸生物合成、多不饱和脂肪酸、磷脂和嘌呤代谢。令人惊讶的是，通过数据挖掘得到的代谢表型关系模式显示，葡萄糖摄入可能会诱导健康组朝着糖尿病状态发展，而在葡萄糖摄入120分钟后，对高果糖饮食喂养的大鼠仅观察到非常轻微的影响。对肝脏、骨骼肌和脑组织的数据处理表明，高果糖饮食在肝脏和骨骼肌组织中导致了氧化应激，如脂质过氧化和抗氧化剂下降、氨基酸升高以及脂肪酸扰动。另一方面，在大脑皮层和海马组织中观察到嘌呤生物合成上调和氨基酸浓度降低。总之，所获得的结果可能不仅为大鼠葡萄糖耐量受损，也为其饮食方式提供新的见解。
High-fructose diet-fed rats as one of the insulin resistant models was used widely for understanding the mechanisms of type 2 diabetes mellitus. Systems-level metabolic profiling of the rat model, however, has not been deciphered clearly. To address this issue, mass spectrometry-based metabolomics was employed to unlock the metabolic snapshots of the oral glucose tolerance test (oGTT) effect in either healthy or diabetic rats, as well as to delineate the metabolic signatures in tissues of rats fed with high-fructose diet. Several differentiating metabolites were highlighted to reveal the metabolic perturbation of the oGTT effects in healthy and diabetic rats, which involved amino acid biosynthesis, polyunsaturated fatty acids, phospholipids and purine metabolism. Surprisingly, the patterns of relationships for the metabolic phenotypes by using data mining revealed that glucose ingestion might induce the healthy group to display its trajectory towards diabetic status, while only a very slight influence was observed on the high-fructose diet-fed rats 120 min after glucose ingestion. The data treatment for liver, skeletal muscle and brain tissues suggested that oxidative stress, such as lipid peroxidation and the declined antioxidant, the elevated amino acids and the perturbation of fatty acids, were caused by the high-fructose diet in liver and skeletal muscle tissues. On the other hand, the up-regulation in purine biosynthesis and the decreased concentrations for amino acids were observed in the cerebral cortex and hippocampus tissues. Collectively, the obtained results might provide a new insight not only for the impairment of glucose tolerance but also for the dietary style in rats.