Alterio Arianna, Alisi Anna, Liccardo Daniela, Nobili Valerio
Hepato-Metabolic Disease Unit and Liver Research Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
Horm Res Paediatr. 2014;82(5):283-9. doi: 10.1159/000365192. Epub 2014 Oct 15.
During the last decade, paediatricians have observed a dramatic increase of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in children. Furthermore, several lines of evidence have reported that a large part of children with NAFLD presents one or more traits of MS making plausible that, in the coming years, these subjects may present a rapid course of disease towards more severe cirrhosis and cardiovascular disease. Genetic susceptibility and the pressure of intrauterine environment and lifestyle are all crucial to activate molecular machinery that leads to development of NAFLD and MS in childhood. In this scenario, central obesity and consequent adipose tissue inflammation are critical to promote both MS-associated metabolic dysfunctions and NAFLD-related hepatic damage. An excessive dietary intake may in fact cause a specific lipid partitioning and induce metabolic stressors, which in turn promote insulin resistance and the release of several circulating factors. These molecules, on the one hand, trigger steatosis and the inflammatory response that characterize liver damage in NAFLD, and on the other hand contribute to the onset of other features of MS. This review provides an overview of current genetic, pathogenetic and clinical evidence of the vicious circle created by NAFLD and MS in children.
在过去十年中,儿科医生观察到儿童非酒精性脂肪性肝病(NAFLD)和代谢综合征(MS)显著增加。此外,有几条证据表明,很大一部分患有NAFLD的儿童表现出一种或多种MS特征,这使得在未来几年,这些儿童可能会迅速发展为更严重的肝硬化和心血管疾病。遗传易感性、子宫内环境压力和生活方式对于激活导致儿童期NAFLD和MS发生的分子机制都至关重要。在这种情况下,中心性肥胖及随之而来的脂肪组织炎症对于促进与MS相关的代谢功能障碍和与NAFLD相关的肝损伤都至关重要。事实上,过量的饮食摄入可能会导致特定的脂质分配并引发代谢应激源,进而促进胰岛素抵抗和多种循环因子的释放。这些分子一方面引发脂肪变性和炎症反应,这些是NAFLD肝损伤的特征,另一方面促成MS其他特征的出现。本综述概述了目前关于儿童NAFLD和MS所形成的恶性循环的遗传、发病机制和临床证据。