Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria-Fundación Hospital La Fe , Valencia, Spain.
J Proteome Res. 2011 Oct 7;10(10):4825-34. doi: 10.1021/pr200629p. Epub 2011 Sep 6.
Steatosis, or excessive accumulation of lipids in the liver, is a generally accepted previous step to the development of more severe conditions like nonalcoholic steatohepatitis, fibrosis, and cirrhosis. We aimed to characterize the metabolic profile that defines simple steatosis in human tissue and to identify potential disturbances in the hepatic metabolism that could favor the switch to progressive liver damage. A total of 46 samples, 23 from steatotic and 23 from nonsteatotic human livers, were analyzed following a holistic LC-MS-based metabonomic analysis that combines RP and HILIC chromatographic separations. Multivariate statistical data analysis satisfactorily classified samples and revealed steatosis-associated biomarkers. Increased levels of bile acids and phospholipid degradation products, and decreased levels of antioxidant species, were found in steatotic livers, indicating disturbances in lipid and bile acid homeostasis and mitochondrial dysfunction. Changes in hypoxanthine, creatinine, glutamate, glutamine, or γ-glutamyl-dipeptides concentrations, suggestive of alterations in energy metabolism and amino acid metabolism and transport, were also found. The results show that the proposed analytical strategy is suitable to achieve a comprehensive metabolic profile of steatotic human liver tissue and provide new insights into the metabolic alterations occurring in fatty liver that could contribute to its predisposition to damage evolution.
脂肪变性，即肝脏内脂质的过度积累，是发展为更严重疾病如非酒精性脂肪性肝炎、纤维化和肝硬化的公认前期步骤。我们旨在描述定义人类组织中单纯性脂肪变性的代谢特征，并确定可能有利于向进行性肝损伤转变的肝代谢中的潜在干扰。总共分析了 46 个样本，其中 23 个来自脂肪变性肝，23 个来自非脂肪变性肝，采用了一种基于 LC-MS 的整体代谢组学分析方法，该方法结合了 RP 和 HILIC 色谱分离。多元统计数据分析令人满意地对样本进行了分类，并揭示了与脂肪变性相关的生物标志物。在脂肪变性的肝脏中发现了胆汁酸和磷脂降解产物水平升高，以及抗氧化物质水平降低，表明脂质和胆汁酸稳态以及线粒体功能障碍受到干扰。还发现了次黄嘌呤、肌酸、谷氨酸、谷氨酰胺或γ-谷氨酰二肽浓度的变化，提示能量代谢和氨基酸代谢和转运发生改变。结果表明，所提出的分析策略适合于实现脂肪变性人类肝组织的全面代谢特征，并提供了对脂肪性肝病中发生的代谢改变的新见解，这些改变可能有助于其对损伤演变的易感性。
