High-Fat Diet Induces Dynamic Metabolic Alterations in Multiple Biological Matrices of Rats
High-Fat Diet Induces Dynamic Metabolic Alterations in Multiple Biological Matrices of Rats
复制标题
高脂肪饮食诱导大鼠多种生物基质的动态代谢变化
DOI：
10.1021/pr400398b
复制
发表时间：
2013-08-01
影响因子：
4.4
通讯作者：
Tang, Huiru
中科院分区：
文献类型：
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作者：
An, Yanpeng;Xu, Wenxin;Tang, Huiru
肥胖是一种由个体生物学和环境因素相互作用引起的疾病，引起多种并发症。为了了解系统的代谢变化与肥胖的发展和进展，我们系统地分析了动态代谢组学的变化，高脂饮食（HFD）诱导的大鼠多种生物基质中使用NMR和GC-FID/MS技术。获得临床化学和组织病理学数据作为补充信息。我们发现，HFD摄入引起血浆、肝脏和尿液样本的系统性代谢变化，涉及多种代谢途径，包括糖酵解、TCA循环和肠道微生物群功能以及脂肪酸、氨基酸、胆碱、B族维生素、嘌呤和嘧啶的代谢。HFD诱导的代谢变化在大鼠摄入HFD一周后的尿液中可检测到，并显示出明显的摄入时间依赖性。B族维生素和肠道微生物群在肥胖的发生和发展中起着重要作用，同时TCA循环中间产物（柠檬酸盐、α-酮戊二酸盐、琥珀酸盐和富马酸盐）也发生了变化。83-日HFD摄入引起大鼠肝脏中显著的代谢改变，突出表现为脂肪生成、脂质积累和脂质氧化的增强、糖酵解的抑制、代谢异生和糖原生成的上调以及胆碱、氨基酸和核苷酸的代谢改变。HFD摄入量降低了血浆和肝脏中PUFA与MUFA的比例，表明HFD诱导的氧化应激。这些发现提供了关于HFD诱导的肥胖的发展和进展的动态代谢反应的基本生物化学信息。本研究还证明了多种生物基质的组合代谢组学分析是了解发病机制和疾病进展的分子基础的有力方法。
Obesity is a condition resulting from the interactions of individual biology and environmental factors causing multiple complications. To understand the system's metabolic changes associated with the obesity development and progression, we systematically analyzed the dynamic metabonomic changes induced by a high-fat diet (HFD) in multiple biological matrices of rats using NMR and GC-FID/MS techniques. Clinical chemistry and histopathological data were obtained as complementary information. We found that HFD intakes caused systematic metabolic changes in blood plasma, liver, and urine samples involving multiple metabolic pathways including glycolysis, TCA cycle, and gut microbiota functions together with the metabolisms of fatty adds, amino adds, choline, B-vitamins, purines, and pyrimidines. The HFD-induced metabolic variations were detectable in rat urine a week after HFD intake and showed clear dependence on the intake duration. B-vitamins and gut microbiota played important roles in the obesity development and progression together with changes in TCA cycle intermediates (citrate, a-ketoglutarate, succinate, and fumarate). 83-day HFD intakes caused significant metabolic alterations in rat liver highlighted with the enhancements in lipogenesis, lipid accumulation and lipid oxidation, suppression of glycolysis, up-regulation of gluconeogenesis and glycogenesis together with altered metabolisms of choline, amino acids and nucleotides. HFD intakes reduced the PUFA-to-MUFA ratio in both plasma and liver, indicating the HFD-induced oxidative stress. These findings provided essential biochemistry information about the dynamic metabolic responses to the development and progression of HFD-induced obesity. This study also demonstrated the combined metabonomic analysis of multiple biological matrices as a powerful approach for understanding the molecular basis of pathogenesis and disease progression.