Butte Nancy F, Liu Yan, Zakeri Issa F, Mohney Robert P, Mehta Nitesh, Voruganti V Saroja, Göring Harald, Cole Shelley A, Comuzzie Anthony G
USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA;
Am J Clin Nutr. 2015 Aug;102(2):256-67. doi: 10.3945/ajcn.115.111872. Epub 2015 Jun 17.
Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity.
We aimed to 1) identify metabolites that differ significantly between nonobese and obese Hispanic children; 2) collapse metabolites into principal components (PCs) associated with obesity and metabolic risk, specifically hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, and hyperuricemia; and 3) identify metabolites associated with energy expenditure and fat oxidation.
This trial was a cross-sectional observational study of metabolomics by using gas chromatography-mass spectrometry and ultrahigh-performance liquid chromatography-tandem mass spectrometry analyses performed on fasting plasma samples from 353 nonobese and 450 obese Hispanic children.
Branched-chained amino acids (BCAAs) (Leu, Ile, and Val) and their catabolites, propionylcarnitine and butyrylcarnitine, were significantly elevated in obese children. Strikingly lower lysolipids and dicarboxylated fatty acids were seen in obese children. Steroid derivatives were markedly higher in obese children as were markers of inflammation and oxidative stress. PC6 (BCAAs and aromatic AAs) and PC10 (asparagine, glycine, and serine) made the largest contributions to body mass index, and PC10 and PC12 (acylcarnitines) made the largest contributions to adiposity. Metabolic risk factors and total energy expenditure were associated with PC6, PC9 (AA and tricarboxylic acid cycle metabolites), and PC10. Fat oxidation was inversely related to PC8 (lysolipids) and positively related to PC16 (acylcarnitines).
Global metabolomic profiling in nonobese and obese children replicates the increased BCAA and acylcarnitine catabolism and changes in nucleotides, lysolipids, and inflammation markers seen in obese adults; however, a strong signature of reduced fatty acid catabolism and increased steroid derivatives may be unique to obese children. Metabolic flexibility in fuel use observed in obese children may occur through the activation of alternative intermediary pathways. Insulin resistance, hyperleptinemia, hypertriglyceridemia, hyperuricemia, and oxidative stress and inflammation evident in obese children are associated with distinct metabolomic profiles.
代谢组学可能揭示儿童肥胖病理生理学中涉及的重要生物学途径。
我们旨在1）鉴定非肥胖和肥胖西班牙裔儿童之间存在显著差异的代谢物；2）将代谢物归纳为与肥胖和代谢风险相关的主成分（PCs），特别是高胰岛素血症、高甘油三酯血症、高瘦素血症和高尿酸血症；3）鉴定与能量消耗和脂肪氧化相关的代谢物。
本试验是一项代谢组学的横断面观察研究，使用气相色谱 - 质谱联用和超高效液相色谱 - 串联质谱分析法，对353名非肥胖和450名肥胖西班牙裔儿童的空腹血浆样本进行分析。
肥胖儿童的支链氨基酸（BCAAs）（亮氨酸、异亮氨酸和缬氨酸）及其分解代谢产物丙酰肉碱和丁酰肉碱显著升高。肥胖儿童的溶血磷脂和二羧酸脂肪酸明显较低。肥胖儿童的类固醇衍生物明显较高，炎症和氧化应激标志物也是如此。PC6（BCAAs和芳香族氨基酸）和PC10（天冬酰胺、甘氨酸和丝氨酸）对体重指数的贡献最大，PC10和PC12（酰基肉碱）对肥胖的贡献最大。代谢风险因素和总能量消耗与PC6、PC9（氨基酸和三羧酸循环代谢物）和PC10相关。脂肪氧化与PC8（溶血磷脂）呈负相关，与PC16（酰基肉碱）呈正相关。
非肥胖和肥胖儿童的整体代谢组学分析重现了肥胖成年人中增加的BCAA和酰基肉碱分解代谢以及核苷酸、溶血磷脂和炎症标志物的变化；然而，脂肪酸分解代谢减少和类固醇衍生物增加的强烈特征可能是肥胖儿童所特有的。肥胖儿童中观察到的燃料利用代谢灵活性可能通过替代中间途径的激活而发生。肥胖儿童中明显的胰岛素抵抗、高瘦素血症、高甘油三酯血症、高尿酸血症以及氧化应激和炎症与不同的代谢组学特征相关。
