Metabolic profiling of livers and blood from obese Zucker rats
Metabolic profiling of livers and blood from obese Zucker rats
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DOI：
10.1016/j.jhep.2005.07.009
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发表时间：
2006-05-01
影响因子：
25.7
通讯作者：
Niemann, CU
中科院分区：
文献类型：
--
作者：
Serkova, NJ;Jackman, M;Niemann, CU
背景/目的：肥胖经常导致脂肪酸代谢发生变化，随后脂肪浸润肝脏。方法：在这项研究中，基于定量核磁共振波谱 (NMR) 分析，建立了瘦和肥胖 Zucker 大鼠的肝脏和血液的代谢谱。结果：肝脏脂质提取物的 H-1 NMR 表明总脂肪酸和甘油三酯的浓度显着增加。肝脏提取物的 P-31 NMR 显示，肥胖肝脏的能量平衡受损（[ATP/ADP] 较低），线粒体活性降低。同时，检测到糖酵解活性增加。最显着的差异是肥胖动物中蛋氨酸的高度增加和甜菜碱浓度的降低。这表明蛋氨酸代谢发生显着改变，这可能是脂肪变性的发生、线粒体功能障碍的诱导以及脂肪肝对缺血/再灌注损伤的脆弱性增加的部分原因。肥胖组存在肝脏谷胱甘肽浓度降低的趋势以及[PUFA/MUFA]比率降低的趋势，表明氧化应激和脂质过氧化增加。结论：总而言之，对肥胖Zucker大鼠的血液和肝脏组织进行NMR分析，揭示了线粒体功能和蛋氨酸代谢的特异性代谢异常，从而导致肝脏能量状态下降。 (c) 2005 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background/Aims: Obesity frequently leads to changes in fatty acid metabolism with subsequent fatty infiltration in the liver.Methods: In this study, metabolic profile of the livers and blood from lean and obese Zucker rats was established based on quantitative nuclear magnetic resonance spectroscopy (NMR) analysis.Results: H-1 NMR on liver lipid extracts indicated significantly increased concentrations of total fatty acids and triglycerides. P-31 NMR on liver extracts revealed that obese livers have a compromised energy balance (low [ATP/ADP]) with decreased mitochondrial activity. Simultaneously, increased glycolytic activity was detected. The most pronounced differences were highly increased methionine and decreased betaine concentrations in obese animals. This suggests a significant alteration in methionine metabolism, which may be in part responsible for the development of steatosis, induction of mitochondrial dysfunction, and increased vulnerability of fatty livers to ischemia/reperfusion injury. A trend towards decreased hepatic glutathione concentrations as well as a reduced [PUFA/MUFA] ratio were present in the obese group, indicating increased oxidative stress and lipid peroxidation.Conclusions: In conclusion, NMR analysis on blood and liver tissue from obese Zucker rats reveals specific metabolic abnormalities in mitochondrial function and methionine metabolism, which result in a decreased hepatic energy state. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.