Discrimination of steatosis and NASH in mice using nuclear magnetic resonance spectroscopy
Discrimination of steatosis and NASH in mice using nuclear magnetic resonance spectroscopy
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DOI：
10.1007/s11306-010-0243-6
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发表时间：
2011-06-01
期刊：
影响因子：
3.6
通讯作者：
Gronwald, Wolfram
中科院分区：
文献类型：
--
作者：
Klein, Matthias S.;Dorn, Christoph;Gronwald, Wolfram
非酒精性脂肪性肝病(NAFLD)是肝功能障碍的常见原因。疾病范围从肝脏脂肪变性到非酒精性脂肪性肝炎(NASH)。本研究的目的是确定单纯性肝脂肪变性和NASH小鼠模型的代谢差异，以区分这两个NAFLD阶段。在12周的时间里，雄性BALB/c小鼠被喂以对照组或两种不同的高脂饮食，分别导致肝脏脂肪变性和NASH。通过对亲脂性和亲水性肝脏提取物和尿样的核磁共振谱的独立成分分析(ICA)来确定代谢差异。ICA的结果清楚地区分了这三个被调查组。亲脂性肝脏提取物中的生物标志物为游离胆固醇、胆固醇酯和脂亚甲基。亲水性肝提取物的识别主要受甜菜碱、葡萄糖和乳酸的调节，而尿中牛磺酸、三甲胺-N-氧化物和三甲胺是最具识别能力的生物标志物。总之，现场尿样的核磁共振代谢物指纹图谱可以无创性地区分脂肪变性和NASH。
Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic dysfunction. The disease spectrum ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The aim of this study was to identify metabolic differences in murine models of simple hepatic steatosis and NASH for the distinction of these NAFLD stages. For 12 weeks, male BALB/c mice were fed either a control or two different high-fat diets leading to hepatic steatosis and NASH, respectively. Metabolic differences were determined by independent component analysis (ICA) of nuclear magnetic resonance (NMR) spectra of lipophilic and hydrophilic liver extracts, and urine specimens. The results from ICA clearly discriminated the three investigated groups. Discriminatory biomarkers in the lipophilic liver extracts were free cholesterol, cholesterol ester and lipid methylene. Discrimination of the hydrophilic liver extracts was mainly mediated by betaine, glucose, and lactate, whereas in urine taurine, trimethylamine-N-oxide, and trimethylamine were the most discriminatory biomarkers. In conclusion, NMR metabolite fingerprinting of spot urine specimens may allow the noninvasive distinction of steatosis and NASH.