应用血浆高分辨代谢组学技术在禁食状态下描绘代谢底物利用情况。
Characterizing substrate utilization during the fasted state using plasma high-resolution metabolomics.
机构信息
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States.
Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States.
出版信息
Nutrition. 2023 Dec;116:112160. doi: 10.1016/j.nut.2023.112160. Epub 2023 Jul 13.
OBJECTIVES
High-resolution metabolomics enables global assessment of metabolites and molecular pathways underlying physiologic processes, including substrate utilization during the fasted state. The clinical index for substrate utilization, respiratory exchange ratio (RER), is measured via indirect calorimetry. The aim of this pilot study was to use metabolomics to identify metabolic pathways and plasma metabolites associated with substrate utilization in healthy, fasted adults.
METHODS
This cross-sectional study included 33 adults (mean age 27.7 ± 4.9 y, mean body mass index 24.8 ± 4 kg/m). Participants underwent indirect calorimetry to determine resting RER after an overnight fast. Untargeted metabolomics was performed on fasted plasma samples using dual-column liquid chromatography and ultra-high-resolution mass spectrometry. Linear regression and pathway enrichment analyses identified pathways and metabolites associated with substrate utilization measured with indirect calorimetry.
RESULTS
RER was significantly associated with 1389 metabolites enriched within 13 metabolic pathways (P < 0.05). Lipid-related findings included general pathways, such as fatty acid activation, and specific pathways, such as C21-steroid hormone biosynthesis and metabolism, butyrate metabolism, and carnitine shuttle. Amino acid pathways included those central to metabolism, such as glucogenic amino acids, and pathways needed to maintain reduction-oxidation reactions, such as methionine and cysteine metabolism. Galactose and pyrimidine metabolism were also associated with RER (all P < 0.05).
CONCLUSIONS
The fasting plasma metabolome reflects the diverse macronutrient pathways involved in carbohydrate, amino acid, and lipid metabolism during the fasted state in healthy adults. Future studies should consider the utility of metabolomics to profile individual nutrient requirements and compare findings reported here to clinical populations.
目的
高分辨率代谢组学能够全面评估生理过程中的代谢物和分子途径，包括空腹状态下的底物利用。底物利用的临床指标是呼吸交换率（RER），通过间接测热法进行测量。本研究旨在利用代谢组学鉴定与健康空腹成年人底物利用相关的代谢途径和血浆代谢物。
方法
本横断面研究纳入了 33 名成年人（平均年龄 27.7 ± 4.9 岁，平均体重指数 24.8 ± 4 kg/m2）。参与者在隔夜禁食后进行间接测热法以确定静息 RER。对空腹血浆样本进行非靶向代谢组学分析，采用双柱液相色谱和超高分辨率质谱。线性回归和途径富集分析鉴定了与间接测热法测量的底物利用相关的途径和代谢物。
结果
RER 与 1389 种代谢物显著相关，这些代谢物富集在 13 条代谢途径中（P < 0.05）。脂质相关的发现包括脂肪酸激活等一般途径，以及甾体激素生物合成和代谢、丁酸盐代谢、肉碱穿梭等特定途径。氨基酸途径包括糖质新生氨基酸等代谢中心途径，以及维持氧化还原反应所需的途径，如蛋氨酸和半胱氨酸代谢。半乳糖和嘧啶代谢也与 RER 相关（均 P < 0.05）。
结论
健康成年人空腹状态下，血浆代谢组学反映了碳水化合物、氨基酸和脂质代谢中涉及的多种宏量营养素途径。未来的研究应考虑代谢组学在描述个体营养需求方面的效用，并将此处报告的结果与临床人群进行比较。
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