Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Brain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Int J Mol Sci. 2020 Feb 13;21(4):1249. doi: 10.3390/ijms21041249.
Rapid lifestyle and dietary changes have contributed to a rise in the global prevalence of metabolic syndrome (MetS), which presents a potential healthcare crisis, owing to its association with an increased burden of multiple cardiovascular and neurological diseases. Prior work has identified the role that genetic, lifestyle, and environmental factors can play in the prevalence of MetS. Metabolomics is an important tool to study alterations in biochemical pathways intrinsic to the pathophysiology of MetS. We undertook a metabolomic study of MetS in serum samples from two ethnically distinct, well-characterized cohorts-the Baltimore Longitudinal Study of Aging (BLSA) from the U.S. and the Tsuruoka Metabolomics Cohort Study (TMCS) from Japan. We used multivariate logistic regression to identify metabolites that were associated with MetS in both cohorts. Among the top 25 most significant (lowest -value) metabolite associations with MetS in each cohort, we identified 18 metabolites that were shared between TMCS and BLSA, the majority of which were classified as amino acids. These associations implicate multiple biochemical pathways in MetS, including branched-chain amino acid metabolism, glutathione production, aromatic amino acid metabolism, gluconeogenesis, and the tricarboxylic acid cycle. Our results suggest that fundamental alterations in amino acid metabolism may be central features of MetS.
快速的生活方式和饮食变化导致代谢综合征(MetS)的全球患病率上升,由于其与多种心血管和神经系统疾病负担增加有关,因此这可能会引发潜在的医疗保健危机。先前的工作已经确定了遗传、生活方式和环境因素在 MetS 患病率中的作用。代谢组学是研究代谢综合征病理生理学内在生化途径变化的重要工具。我们对来自两个种族不同、特征明确的队列的血清样本进行了代谢组学研究——美国巴尔的摩纵向衰老研究(BLSA)和日本鹤冈代谢组学队列研究(TMCS)。我们使用多变量逻辑回归来识别与两个队列中的 MetS 相关的代谢物。在每个队列中与 MetS 相关性最高的前 25 个(最低值)代谢物关联中,我们在 TMCS 和 BLSA 之间确定了 18 个代谢物具有相关性,其中大多数被归类为氨基酸。这些关联表明 MetS 涉及多个生化途径,包括支链氨基酸代谢、谷胱甘肽生成、芳香族氨基酸代谢、糖异生和三羧酸循环。我们的研究结果表明,氨基酸代谢的基本变化可能是 MetS 的核心特征。