PURPOSE Nonalcoholic fatty liver disease (NAFLD) is defined by excessive lipid accumulation in the liver and involves an ample spectrum of liver diseases, ranging from simple uncomplicated steatosis to cirrhosis and hepatocellular carcinoma. Accumulating evidence demonstrates that high fructose intake enhances NAFLD development and progression promoting inhibition of mitochondrial β-oxidation of long-chain fatty acids and oxidative damages. L-Carnitine (LC), involved in β-oxidation, has been used to reduce obesity caused by high-fat diet, which is beneficial to ameliorating fatty liver diseases. Moreover, in the recent years, various studies have established LC anti-oxidative proprieties. The objective of this study was to elucidate primarily the underlying anti-oxidative mechanisms of LC in an in vitro model of fructose-induced liver steatosis. METHODS Human hepatoma HepG2 cells were maintained in medium supplemented with LC (5 mM LC) with or without 5 mM fructose (F) for 48 h and 72 h. In control cells, LC or F was not added to medium. Fat deposition, anti-oxidative, and mitochondrial homeostasis were investigated. RESULTS LC supplementation decreased the intracellular lipid deposition enhancing AMPK activation. However, compound C (AMPK inhibitor-10 μM), significantly abolished LC benefits in F condition. Moreover, LC, increasing PGC1 α expression, ameliorates mitochondrial damage-F induced. Above all, LC reduced ROS production and simultaneously increased protein content of antioxidant factors, SOD2 and Nrf2. CONCLUSION Our data seemed to show that LC attenuate fructose-mediated lipid accumulation through AMPK activation. Moreover, LC counteracts mitochondrial damages and reactive oxygen species production restoring antioxidant cellular machine. These findings provide new insights into LC role as an AMPK activator and anti-oxidative molecule in NAFLD.

中文翻译：

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左旋肉碱通过靶向氧化应激标志物对抗体外果糖诱导的肝脂肪变性。

目的 非酒精性脂肪性肝病 (NAFLD) 的定义是肝脏中过多的脂质积累，涉及范围广泛的肝脏疾病，从简单的单纯性脂肪变性到肝硬化和肝细胞癌。越来越多的证据表明，高果糖摄入可促进 NAFLD 的发展和进展，促进抑制长链脂肪酸的线粒体 β-氧化和氧化损伤。左旋肉碱（LC）参与β-氧化，已被用于减少高脂饮食引起的肥胖，有利于改善脂肪肝疾病。此外，近年来，各种研究已经确立了 LC 的抗氧化特性。本研究的目的是在果糖诱导的肝脂肪变性体外模型中主要阐明 LC 的潜在抗氧化机制。方法 人肝癌 HepG2 细胞在补充有 LC (5 mM LC) 的培养基中培养 48 小时和 72 小时。在对照细胞中，未将 LC 或 F 添加到培养基中。研究了脂肪沉积、抗氧化和线粒体稳态。结果 LC 补充剂减少了细胞内脂质沉积，增强了 AMPK 活化。然而，化合物 C (AMPK inhibitor-10 μM) 显着消除了 F 条件下的 LC 益处。此外，LC，增加 PGC1 α 表达，改善线粒体损伤-F 诱导。最重要的是，LC 减少了 ROS 的产生，同时增加了抗氧化因子 SOD2 和 Nrf2 的蛋白质含量。结论 我们的数据似乎表明，LC 通过 AMPK 激活减弱果糖介导的脂质积累。而且，LC 抵消线粒体损伤和活性氧物质的产生，恢复抗氧化细胞机器。这些发现为 LC 作为 AMPK 激活剂和抗氧化分子在 NAFLD 中的作用提供了新的见解。