Division of Pediatric Endocrinology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Nutrients. 2023 Mar 31;15(7):1726. doi: 10.3390/nu15071726.
Despite the importance of hypercholesterolemia in children, it is overlooked, and there are currently few metabolomics-based approaches available to understand its molecular mechanisms. Children from a birth cohort had their cholesterol levels measured with the aim of identifying the metabolites for the molecular biological pathways of childhood hypercholesterolemia. One hundred and twenty-five children were enrolled and stratified into three groups according to cholesterol levels (acceptable, <170 mg/dL, = 42; borderline, 170-200 mg/dL, = 52; and high, >200 mg/dL, = 31). Plasma metabolomic profiles were obtained by using H-nuclear magnetic resonance (NMR) spectroscopy, and partial least squares-discriminant analysis (PLS-DA) was applied using the MetaboAnalyst 5.0 platform. Metabolites significantly associated with different cholesterol statuses were identified, and random forest classifier models were used to rank the importance of these metabolites. Their associations with serum lipid profile and functional metabolic pathways related to hypercholesterolemia were also assessed. Cholesterol level was significantly positively correlated with LDL-C and Apo-B level, as well as HDL-C and Apo-A1 level separately, whereas HDL-C was negatively correlated with triglyceride level ( < 0.01). Eight metabolites including tyrosine, glutamic acid, ornithine, lysine, alanine, creatinine, oxoglutaric acid, and creatine were significantly associated with the different statuses of cholesterol level. Among them, glutamic acid and tyrosine had the highest importance for different cholesterol statuses using random forest regression models. Carbohydrate and amino acid metabolisms were significantly associated with different cholesterol statuses, with glutamic acid being involved in all amino acid metabolic pathways (FDR-adjusted < 0.01). Hypercholesterolemia is a significant health concern among children, with up to 25% having high cholesterol levels. Glutamic acid and tyrosine are crucial amino acids in lipid metabolism, with glutamic-acid-related amino acid metabolism playing a significant role in regulating cholesterol levels.
尽管儿童高胆固醇血症很重要，但却被忽视了，目前可用的基于代谢组学的方法很少，无法了解其分子机制。本研究对一个出生队列的儿童进行了胆固醇水平测量，目的是确定儿童高胆固醇血症分子生物学途径的代谢产物。共纳入 125 名儿童，根据胆固醇水平将其分为三组（可接受水平，<170mg/dL，n=42；边缘水平，170-200mg/dL，n=52；高胆固醇水平，>200mg/dL，n=31）。采用 H-核磁共振（NMR）光谱法获得血浆代谢组学图谱，并应用 MetaboAnalyst 5.0 平台进行偏最小二乘判别分析（PLS-DA）。鉴定出与不同胆固醇状态显著相关的代谢物，并使用随机森林分类器模型对这些代谢物的重要性进行排序。还评估了它们与血清脂质谱的相关性以及与高胆固醇血症相关的功能代谢途径。胆固醇水平与 LDL-C 和 Apo-B 水平呈显著正相关，与 HDL-C 和 Apo-A1 水平分别呈显著负相关，而 HDL-C 与甘油三酯水平呈负相关（<0.01）。有 8 种代谢物（酪氨酸、谷氨酸、鸟氨酸、赖氨酸、丙氨酸、肌酸酐、草酰乙酸和肌酸）与胆固醇水平的不同状态显著相关。其中，谷氨酸和酪氨酸在使用随机森林回归模型时对不同胆固醇状态的重要性最高。碳水化合物和氨基酸代谢与胆固醇水平的不同状态显著相关，谷氨酸参与所有氨基酸代谢途径（FDR 调整后<0.01）。高胆固醇血症是儿童的一个重大健康问题，高达 25%的儿童胆固醇水平较高。谷氨酸和酪氨酸是脂质代谢中关键的氨基酸，谷氨酸相关的氨基酸代谢在调节胆固醇水平方面起着重要作用。
