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.

非酒精性脂肪肝疾病（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堆积（脂肪变性）到非酒精性脂肪性肝炎（NASH），以及可能发展为肝细胞癌和肝衰竭的肝硬化。质谱和磁共振波谱耦合的基于同位素的稳定通量研究为了解NAFLD发病机理和疾病进展提供了新的见识。这篇综述主要集中在基于质谱的方法的利用上，以了解NAFLD不同阶段的代谢异常。例如，基于同位素的稳定通量研究表明，多器官胰岛素抵抗，葡萄糖失调，NAFLD患者的血脂和脂蛋白代谢。我们还将回顾基于同位素的稳定技术的最新进展，以研究NAFLD中的线粒体功能障碍，氧化应激和纤维生成。我们强调了当前方法学的局限性，讨论了该领域的新兴研究领域，以及应用稳定同位素研究NAFLD及其并发症的未来方向。