Diabetes and Fibrotic Disease Unit, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, 85004, USA.
Cell Mol Life Sci. 2020 Jun;77(11):2079-2090. doi: 10.1007/s00018-019-03390-0.
Nonalcoholic fatty liver disease (NAFLD) is a chronic, frequently progressive condition that develops in response to excessive hepatocyte fat accumulation (i.e., steatosis) in the absence of significant alcohol consumption. Liver steatosis develops as a result of imbalanced lipid metabolism, driven largely by increased rates of de novo lipogenesis and hepatic fatty acid uptake and reduced fatty acid oxidation and/or disposal to the circulation. Fructose is a naturally occurring simple sugar, which is most commonly consumed in modern diets in the form of sucrose, a disaccharide comprised of one molecule of fructose covalently bonded with one molecule of glucose. A number of observational and experimental studies have demonstrated detrimental effects of dietary fructose consumption not only on diverse metabolic outcomes such as insulin resistance and obesity, but also on hepatic steatosis and NAFLD-related fibrosis. Despite the compelling evidence that excessive fructose consumption is associated with the presence of NAFLD and may even promote the development and progression of NAFLD to more clinically severe phenotypes, the molecular mechanisms by which fructose elicits effects on dysregulated liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. The aim of this review is to summarize the current research supporting a role for dietary fructose intake in the modulation of transcriptomic and epigenetic mechanisms underlying the pathogenesis of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种慢性、常进行性疾病，发生于在无明显饮酒的情况下肝细胞脂肪过度堆积（即脂肪变性）时。肝脂肪变性是由于脂质代谢失衡所致，主要是由于新生脂肪合成和脂肪酸摄取增加，以及脂肪酸氧化和/或向循环中排泄减少所致。果糖是一种天然存在的简单糖，在现代饮食中最常以蔗糖的形式摄入，蔗糖是由一分子果糖与一分子葡萄糖共价键合而成的二糖。一些观察性和实验性研究表明，饮食中果糖的摄入不仅对胰岛素抵抗和肥胖等多种代谢结果产生有害影响，而且对肝脂肪变性和 NAFLD 相关纤维化也有影响。尽管有令人信服的证据表明，过量摄入果糖与 NAFLD 的存在有关，甚至可能促进 NAFLD 向更严重的临床表型发展，但果糖对失调的肝脏代谢产生影响的分子机制尚不清楚。新出现的数据表明，饮食中的果糖可能直接改变参与脂质代谢的基因的表达，包括那些增加肝脂肪堆积或减少肝脂肪清除的基因。本综述的目的是总结目前支持饮食果糖摄入在调节 NAFLD 发病机制中的转录组学和表观遗传学机制的研究。
