Perla Francesco Massimo, Prelati Maurizia, Lavorato Michela, Visicchio Daniele, Anania Caterina
Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, 00161, Italy.
Children (Basel). 2017 Jun 6;4(6):46. doi: 10.3390/children4060046.
Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a "multiple-hit process" where the first "hit" is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD.
由于全球肥胖症的流行，非酒精性脂肪性肝病（NAFLD）已成为儿童和青少年中最普遍的慢性肝脏疾病之一。NAFLD包括一系列与脂肪相关的肝脏疾病，这些疾病可能导致终末期肝病并需要进行肝移植。单纯性脂肪变性，即脂肪肝，在NAFLD早期出现，并可能进展为非酒精性脂肪性肝炎、纤维化和肝硬化，同时肝细胞癌风险增加。目前认为，NAFLD中肝损伤的机制是一个“多重打击过程”，其中第一次“打击”是肝脏脂肪增加，随后是多个引发炎症活动的其他因素。在疾病发作时，NAFLD的特征是肝内甘油三酯积累和胰岛素抵抗。肝脏脂肪积累与高水平游离脂肪酸、游离胆固醇和其他脂质代谢产物导致的脂毒性增加有关。因此，会激活伴有氧化应激和活性氧产生的线粒体功能障碍以及内质网应激相关机制。本综述重点关注细胞内脂质积累与胰岛素抵抗之间的关系，以及NAFLD中的脂质和脂蛋白代谢。
