Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People's Republic of China.
Acta Pharmacol Sin. 2011 Feb;32(2):270-8. doi: 10.1038/aps.2010.196.
To explore the alteration of endogenous metabolites and identify potential biomarkers using metabolomic profiling with gas chromatography coupled a time-of-flight mass analyzer (GC/TOF-MS) in a rat model of estrogen-deficiency-induced obesity.
Twelve female Sprague-Dawley rats six month of age were either sham-operated or ovariectomized (OVX). Rat blood was collected, and serum was analyzed for biomarkers using standard colorimetric methods with commercial assay kits and a metabolomic approach with GC/TOF-MS. The data were analyzed using multivariate statistical techniques.
A high body weight and body mass index inversely correlated with serum estradiol (E2) in the OVX rats compared to the sham rats. Estrogen deficiency also significantly increased serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Utilizing GC/TOF-MS-based metabolomic analysis and the partial least-squares discriminant analysis, the OVX samples were discriminated from the shams. Elevated levels of cholesterol, glycerol, glucose, arachidonic acid, glutamic acid, glycine, and cystine and reduced alanine levels were observed. Serum glucose metabolism, energy metabolism, lipid metabolism, and amino acid metabolism were involved in estrogen-deficiency-induced obesity in OVX rats.
The series of potential biomarkers identified in the present study provided fingerprints of rat metabolomic changes during obesity and an overview of multiple metabolic pathways during the progression of obesity involving glucose metabolism, lipid metabolism, and amino acid metabolism.
利用气相色谱-飞行时间质谱联用仪(GC/TOF-MS)代谢组学分析,探讨雌激素缺乏诱导肥胖大鼠模型中内源性代谢物的变化,并寻找潜在的生物标志物。
将 12 只 6 月龄雌性 Sprague-Dawley 大鼠分为假手术组或卵巢切除术(OVX)组。采集大鼠血液,采用标准比色法和 GC/TOF-MS 代谢组学方法分析血清生物标志物。采用多元统计技术分析数据。
与假手术组大鼠相比,OVX 大鼠体重和体重指数较高,血清雌二醇(E2)水平较低。雌激素缺乏还显著增加了血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇。利用基于 GC/TOF-MS 的代谢组学分析和偏最小二乘判别分析,OVX 组样本与假手术组样本得以区分。结果显示,胆固醇、甘油、葡萄糖、花生四烯酸、谷氨酸、甘氨酸和胱氨酸水平升高,丙氨酸水平降低。血清葡萄糖代谢、能量代谢、脂质代谢和氨基酸代谢参与了 OVX 大鼠雌激素缺乏诱导的肥胖。
本研究中鉴定的一系列潜在生物标志物为肥胖大鼠代谢组学变化提供了特征图谱,并概述了涉及葡萄糖代谢、脂质代谢和氨基酸代谢的肥胖进展过程中的多种代谢途径。