Metabolomic Analysis of Livers and Serum from High-Fat Diet Induced Obese Mice
Metabolomic Analysis of Livers and Serum from High-Fat Diet Induced Obese Mice
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DOI：
10.1021/pr100892r
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发表时间：
2011-02-01
影响因子：
4.4
通讯作者：
Yoon, Suk Hoo
中科院分区：
文献类型：
--
作者：
Kim, Hyun-Jin;Kim, Jin Hee;Yoon, Suk Hoo
采用超高效液相色谱-四极杆-飞行时间质谱法、气相色谱-质谱法和偏最小二乘判别分析法（PLS-DA）对高脂或正常饮食喂养的肥胖和瘦小鼠的肝脏和血清代谢物进行了分析。在PLS-DA评分图上，肥胖组和瘦组彼此明显区分，并且有助于区分的主要代谢物被分配为脂质代谢物（脂肪酸、磷脂酰胆碱（PC）和溶血磷脂酰胆碱（lysoPC））、脂质代谢中间体（甜菜碱、肉毒碱和酰基肉毒碱）、氨基酸、酸性化合物、单糖和5-羟色胺。高脂饮食增加了脂质代谢产物，但降低了脂质代谢中间产物和NAD/NADH比值，表明高脂饮食诱导的脂质和能量代谢异常通过降低β-氧化导致脂肪蓄积。此外，这项研究揭示了许多代谢物的水平，包括血清素，甜菜碱，哌啶酸和尿酸，与肥胖相关疾病呈正或负相关。根据这些代谢产物，我们提出了一个与高脂饮食诱导肥胖相关的代谢途径。这些代谢物可用于更好地了解由高脂饮食引起的肥胖和相关疾病。此外，这些代谢物的水平变化可用于评估肥胖的风险和肥胖管理的治疗效果。
Liver and serum metabolites of obese and lean mice fed on high fat or normal diets were analyzed using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry, gas chromatography mass spectrometry, and partial least-squares-discriminant analysis (PLS-DA). Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids, phosphatidylcholines (PCs), and lysophosphatidylcholines (lysoPCs)), lipid metabolism intermediates (betaine, carnitine, and acylcarnitines), amino acids, acidic compounds, monosaccharides, and serotonin. A high-fat diet increased lipid metabolites but decreased lipid metabolism intermediates and the NAD/NADH ratio, indicating that abnormal lipid and energy metabolism induced by a high-fat diet resulted in fat accumulation via decreased beta-oxidation. In addition, this study revealed that the levels of many metabolites, including serotonin, betaine, pipecolic acid, and uric acid, were positively or negatively related to obesity-associated diseases. On the basis of these metabolites, we proposed a metabolic pathway related to high-fat diet-induced obesity. These metabolites can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.