Abstract
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 p-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.
Highlights
Metabolic syndrome (MetS) is a cluster of risk factors that raises an individual’s risk for heart disease, diabetes, stroke, and chronic neurodegenerative disease [1,2,3,4]
The prevalence of MetS was similar between groups, but Baltimore Longitudinal Study of Aging (BLSA) participants had a greater prevalence of elevated triglycerides and reduced high-density lipoprotein (HDL)-C
Tsuruoka Metabolomics Cohort Study (TMCS) participants had a greater prevalence of elevated waist circumference, elevated fasting glucose, and elevated blood pressure
Summary
Metabolic syndrome (MetS) is a cluster of risk factors that raises an individual’s risk for heart disease, diabetes, stroke, and chronic neurodegenerative disease [1,2,3,4]. MetS is defined as having 3 or more of 5 individual risk factors including elevated waist circumference, fasting serum/plasma glucose concentration, triglyceride levels, and blood pressure and reduced serum/plasma high-density lipoprotein (HDL) cholesterol [5]. In the United States, more than one-third of adults and more than one-half of those 60 years or older have MetS [6]. In Japan, for instance, government estimates suggest that nearly one-third of males and one-tenth of females 20 years or older have MetS and expectations suggest that the prevalence will likely increase in the coming years [9]. Presence of MetS further inflates the per-patient cost of treatment for those with hypertension, and overall patient-specific health costs increase with the accumulation of each additional MetS risk factor [10]
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