Blood Metabolite Signature of Metabolic Syndrome Implicates Alterations in Amino Acid Metabolism: Findings from the Baltimore Longitudinal Study of Aging (BLSA) and the Tsuruoka Metabolomics Cohort Study (TMCS)

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.

The prebiotic effects of omega-3 fatty acid supplementation: A six-week randomised intervention trial

“…Certain gut-derived metabolites such as TMAO and IPA were measured using tandem mass spectrometry with the Biocrates MxP Qaunt 500 kit (Biocrates Life Science AG, Innsbruck, Austria). 34 …”

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…As an example, the gut microbiome product TMAO has been considered a shared risk factor between numerous diseases, such as IR, cancer, Alzheimer's disease (AD) and schizophrenia, among others [238,239]. Clinical studies have described that higher circulating levels of TMAO are correlated with a higher inflammatory response (↑ C-reactive protein, ↑ TNF-α, ↑ IL-6) [240].…”

A brain proteomic signature of incipient Alzheimer’s disease in youngAPOEε4 carriers identifies novel drug targets

“…The coefficient of interest was protein * time: A significant ( P < 0.05) positive coefficient indicated that higher concentration of the protein was associated with slower/reduced decline in MMSE over time; a significant ( P < 0.05) negative coefficient indicated that increased concentration of the protein was associated with faster increased decline in MMSE over time. Similar to previous analyses ( 76 ), protein concentration (predictor) was centered at the median, rescaled using the interquartile range (IQR), and outliers greater than 3 * IQR were excluded. Age of death was mean-centered, and sex was coded 0 as male and 1 as female.…”