Fu Kangning, Yan Xing, Chen Lizhu, Wang Hechen, Lai Qiong, Li Linnan, Wang Zhengtao, Wang Rui, Ding Lili, Yang Li
The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China.
J Pharm Biomed Anal. 2025 Nov 15;265:116989. doi: 10.1016/j.jpba.2025.116989. Epub 2025 May 27.
The central carbon energy metabolism, which is crucial to the metabolic pathway in almost all living organisms and in the regulation of responses to various kinds of stress. Most of serious metabolic disorders in basic life activities of life are attributed to energy metabolism disorders. Metabolic dysfunction-associated fatty liver disease (MAFLD) and other metabolic disease are usually accompanied with the disturbance of energy metabolism. Maintaining energy homeostasis is crucial for overall health and even survival. To date, there is no systematic study on energy metabolites profile of MAFLD. In this study, we established a method for the simultaneous quantification of 31 endogenous metabolites involved three pathways in the tricarboxylic acid (TCA) cycle, glycolysis and oxidative phosphorylation metabolic pathway by using the UPLC-MS/MS system. This present method offers significant advantages including simple and fast preparation of a wide range of mice and human biological samples and was successfully validated with satisfactory linearity, sensitivity, accuracy, precision, matrix effects, recovery and stability. Target metabolomics analysis was performed in different tissues and organs of mice and the substantial metabolic disparity among mice and human was demonstrated, further verifying the applicability and reliability of our method. Multivariate statistical analysis approach was conducted on 31 variables in human and mice serum samples. Based on VIP> 1, P value< 0.05, seven differential metabolites were screened out for MAFLD in human and mice. ROC analysis indicated that the seven potential markers provided a good diagnostic efficiency for MAFLD. The method demonstrated a simple and promising strategy to rapidly determine the energy metabolism status in mice and human, which can provide valuable results for mechanistic studies. This work provides metabolomic information for the study of metabolic diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to energy metabolism in medical institutions.
中心碳能量代谢，对几乎所有生物体的代谢途径以及对各种应激反应的调节都至关重要。生命基本活动中的大多数严重代谢紊乱都归因于能量代谢紊乱。代谢功能障碍相关脂肪性肝病（MAFLD）和其他代谢性疾病通常伴随着能量代谢紊乱。维持能量稳态对整体健康乃至生存至关重要。迄今为止，尚未有关于MAFLD能量代谢物谱的系统研究。在本研究中，我们建立了一种方法，通过超高效液相色谱-串联质谱（UPLC-MS/MS）系统同时定量三羧酸（TCA）循环、糖酵解和氧化磷酸化代谢途径中涉及的31种内源性代谢物。该方法具有显著优势，包括简单快速地制备多种小鼠和人类生物样本，并成功验证了其具有令人满意的线性、灵敏度、准确性、精密度、基质效应、回收率和稳定性。在小鼠的不同组织和器官中进行了靶向代谢组学分析，证明了小鼠和人类之间存在显著的代谢差异，进一步验证了我们方法的适用性和可靠性。对人类和小鼠血清样本中的31个变量进行了多元统计分析。基于VIP>1、P值<0.05，筛选出了7种人类和小鼠MAFLD的差异代谢物。ROC分析表明，这7种潜在标志物对MAFLD具有良好的诊断效率。该方法展示了一种简单且有前景的策略，可快速确定小鼠和人类的能量代谢状态，能为机制研究提供有价值的结果。这项工作为代谢性疾病的研究提供了代谢组学信息，为医疗机构中与能量代谢相关的临床靶点分析和疗效评估提供了分析方法。
