背景:儿童肥胖仍然是一个关键的公共健康问题,对人们的健康具有深远的影响。
目的:本研究旨在调查血浆和粪便中的代谢物与包括体重指数(BMI)在内的指标之间的关联。BMI为年龄Z评分(BMIZ),中国6-9岁儿童的体脂分布。
方法:这项横断面研究纳入了424名健康儿童,其中包括186名女孩和238名男孩。使用双能X射线吸收法(DXA)确定体脂含量和区域脂肪分布。使用靶向代谢组学技术分析血浆和粪便代谢物。
结果:通过超高效液相色谱与串联质谱(UPLC-MS/MS)对总共200种血浆代谢物和212种粪便代谢物进行了准确定量。利用正交投影进行潜在结构判别分析(OPLS-DA)和随机森林模型,我们发现9种血浆代谢物和11种粪便代谢物与不同的体重状态相关.在调整潜在协变量和错误发现率(FDR)校正后,多元线性回归分析显示,血浆代谢物(富马酸,甘氨酸,l-谷氨酰胺,甲基丙二酸,和琥珀酸)和粪便代谢物(原儿茶酸)呈负相关(β:-1.373--0.016,pFDR:<0.001-0.031;β:-1.008--0.071,pFDR:0.005-0.033),而血浆代谢物(异戊酸,异戊酰基肉碱,l-谷氨酸,和焦谷氨酸)和粪便代谢物(3-氨基异丁酸,丁酸,N-乙酰神经氨酸,辛酰基肉碱,油酰肉碱,棕榈酰肉碱,硬脂酰肉碱,牛磺鹅脱氧胆酸,牛磺脱氧胆酸)与BMI呈正相关,BMIZ,和体脂分布(β:0.023-2.396,pFDR:<0.001;β:0.014-1.736,pFDR:<0.001-0.049)。
结论:血浆和粪便代谢产物如谷氨酰胺可能作为肥胖发展的潜在治疗靶点。
BACKGROUND: Childhood obesity continues to be a critical public health concern with far-reaching implications for the well-being.
OBJECTIVE: This study aimed to investigate the association between metabolites in plasma and feces and indicators including body mass index (BMI), BMI for age Z score (BMIZ), and body fat distribution among children aged 6-9 years in China.
METHODS: This cross-sectional study enrolled 424 healthy children, including 186 girls and 238 boys. Dual-energy X-ray absorptiometry (DXA) was used to determine the body fat content and regional fat distribution. Plasma and fecal metabolites were analyzed using targeted metabolomic technologies.
RESULTS: A total of 200 plasma metabolites and 212 fecal metabolites were accurately quantified via ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). By using Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and random forest model, we discovered that 9 plasma metabolites and 11 fecal metabolites were associated with different weight statuses. After adjusting for potential covariates and false discovery rate (FDR) correction, multiple linear regression analyses revealed that plasma metabolites (fumaric acid, glycine, l-glutamine, methylmalonic acid, and succinic acid) and fecal metabolites (protocatechuic acid) were negatively associated (β: -1.373--0.016, pFDR: <0.001-0.031; β: -1.008--0.071, pFDR: 0.005-0.033), while plasma metabolites (isovaleric acid, isovalerylcarnitine, l-glutamic acid, and pyroglutamic acid) and fecal metabolites (3-aminoisobutanoic acid, butyric acid, N-acetylneuraminic acid, octanoylcarnitine, oleoylcarnitine, palmitoylcarnitine, stearoylcarnitine, taurochenodesoxycholic acid, and taurodeoxycholic acid) exhibited positive associations with BMI, BMIZ, and body fat distribution (β: 0.023-2.396, pFDR: <0.001; β: 0.014-1.736, pFDR: <0.001-0.049).
CONCLUSIONS: Plasma and fecal metabolites such as glutamine may serve as a potential therapeutic target for the development of obesity.