Ariz Usue, Mato Jose Maria, Lu Shelly C, Martínez Chantar Maria L
Metabolomics, Parque Technológico de Bizkaia, Derio, Spain.
Methods Mol Biol. 2010;593:109-36. doi: 10.1007/978-1-60327-194-3_6.
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological term that encompasses a spectrum of abnormalities ranging from simple triglyceride accumulation in the hepatocytes (hepatic steatosis) to hepatic steatosis with inflammation (steatohepatitis, also known as nonalcoholic steatohepatitis or NASH). NASH can also progress to cirrhosis and hepatocellular carcinoma (HCC). Steatohepatitis has been estimated to affect around 5% of the total population and 20% of those who are overweight. The mechanisms leading to NASH and its progression to cirrhosis and HCC remain unclear, but it is a condition typically associated with obesity, insulin resistance, diabetes, and hypertriglyceridemia. This point corroborates the need for animal models and molecular markers that allow us to understand the mechanisms underlying this disease. Nowadays, there are numerous mice models to study abnormal liver function such as steatosis, NASH, and hepatocellular carcinoma. The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis, although these remain incompletely understood and no mice model completely fulfills the clinical features observed in humans. In addition, there is a lack of accurate sensitive diagnostic tests that do not involve invasive procedures. Current laboratory tests include some biochemical analysis, but their utility for diagnosing NASH is still poor. For that reason, a great effort is being made toward the identification and validation of novel biomarkers to assess NASH using high-throughput analysis based on genomics, proteomics, and metabolomics. The most recent discoveries and their validation will be discussed.
非酒精性脂肪性肝病（NAFLD）是一个临床病理学术语，涵盖了一系列异常情况，从肝细胞内单纯的甘油三酯蓄积（肝脂肪变性）到伴有炎症的肝脂肪变性（脂肪性肝炎，也称为非酒精性脂肪性肝炎或NASH）。NASH也可进展为肝硬化和肝细胞癌（HCC）。据估计，脂肪性肝炎影响约5%的总人口以及20%的超重人群。导致NASH及其进展为肝硬化和HCC的机制尚不清楚，但这是一种通常与肥胖、胰岛素抵抗、糖尿病和高甘油三酯血症相关的病症。这一点证实了需要动物模型和分子标志物来帮助我们理解该疾病的潜在机制。如今，有许多小鼠模型用于研究异常肝功能，如肝脂肪变性、NASH和肝细胞癌。对已建立的动物模型的研究在肝脂肪变性和脂肪性肝炎的发病机制方面提供了许多线索，尽管这些机制仍未完全明确，且没有小鼠模型能完全符合人类所观察到的临床特征。此外，缺乏不涉及侵入性操作的准确灵敏的诊断测试。目前的实验室检测包括一些生化分析，但其对NASH的诊断效用仍然很差。因此，人们正在大力致力于通过基于基因组学、蛋白质组学和代谢组学的高通量分析来鉴定和验证用于评估NASH的新型生物标志物。将讨论最新的发现及其验证情况。
