Stable isotope-based flux studies in nonalcoholic fatty liver disease.
Stable isotope-based flux studies in nonalcoholic fatty liver disease.
复制标题
非酒精性脂肪肝疾病中基于稳定同位素的通量研究。
DOI：
10.1016/j.pharmthera.2017.07.008
复制
发表时间：
2018
影响因子：
13.5
通讯作者：
Kasumov,Takhar
中科院分区：
文献类型：
--
作者：
McCullough,Arthur;Previs,Stephen;Kasumov,Takhar
非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病，与肥胖、糖尿病和心血管疾病的全球流行有关。NAFLD的范围从肝脏中的良性脂肪积累（脂肪变性）到非酒精性脂肪性肝炎（NASH），以及可发展为肝细胞癌和肝功能衰竭的肝硬化。质谱和磁共振谱耦合稳定同位素通量研究为NAFLD的发病机制和疾病进展提供了新的认识。本文主要综述了基于质谱的方法在NAFLD不同阶段代谢异常的应用。例如，基于稳定同位素的通量研究表明，NAFLD患者存在多器官胰岛素抵抗、葡萄糖、脂质和脂蛋白代谢紊乱。我们还回顾了稳定同位素技术在NAFLD线粒体功能障碍、氧化应激和纤维化研究中的最新进展。我们强调了当前方法的局限性，讨论了该领域的新兴研究领域，以及稳定同位素应用于研究NAFLD及其并发症的未来方向。
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression. This review focuses mainly on the utilization of mass spectrometry-based methods for the understanding of metabolic abnormalities in the different stages of NAFLD. For example, stable isotope-based flux studies demonstrated multi-organ insulin resistance, dysregulated glucose, lipids and lipoprotein metabolism in patients with NAFLD. We also review recent developments in the stable isotope-based technologies for the study of mitochondrial dysfunction, oxidative stress and fibrogenesis in NAFLD. We highlight the limitations of current methodologies, discuss the emerging areas of research in this field, and future directions for the applications of stable isotopes to study NAFLD and its complications.