Institute of Metabolic Science.
Core Metabolomics and Lipidomics Laboratory, Wellcome Trust-MRC institute of Metabolic Science, University of Cambridge, Cambridge.
J Pediatr Gastroenterol Nutr. 2022 Jun 1;74(6):734-741. doi: 10.1097/MPG.0000000000003418. Epub 2022 Feb 19.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterised by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease.
We performed untargeted liquid chromatography-mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9500 adults with metabolic phenotyping.
More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (pC) and triglycerides (TG). Similar trends in pC and TG chain length and saturation were seen in adults with hepatic steatosis; however, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants.
These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.
非酒精性脂肪性肝病（NAFLD）是一种在儿童中越来越常见的疾病，其特征为胰岛素抵抗和脂质代谢改变。受影响的患者心血管疾病（CVD）风险增加，且患有 NAFLD 的儿童可能有过早发生心脏事件的风险。评估 NAFLD 患儿的血浆脂质谱可提供研究这些改变的机会，并了解其与患有代谢性心血管疾病的成年人的改变有多么相似。
我们对 287 名儿童进行了非靶向液相色谱-质谱（LC-MS）血浆脂质组学分析：19 名瘦对照组、146 名肥胖组和 122 名接受肝活检的 NAFLD 病例。使用回归分析调整年龄和性别后，评估了脂质种类与肝组织学之间的相关性。然后使用代谢表型 9500 名成年人的数据进行了结果复制。
更严重的儿科 NAFLD 与长链、多不饱和磷脂酰胆碱（pC）和甘油三酯（TG）水平降低相关。在患有肝脂肪变性的成年人中，pC 和 TG 链长和饱和度也存在类似的趋势；然而，与 NAFLD 相关的许多特定脂质在儿童和成年人之间存在差异。在成年人中复制的 5 种脂质（包括 PC（36：4））与死亡和代谢性心血管疾病直接相关，也通过遗传变异间接相关。
这些发现表明，尽管儿科 NAFLD 与成年人代谢性心血管疾病中脂质代谢的相似途径受到干扰，但儿童的特定脂质特征不同。
