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)
by
Jackson A. Roberts 1
, Vijay R. Varma 1, Chiung-Wei Huang 2, Yang An 2, Anup Oommen 3, Toshiko Tanaka 4, Luigi Ferrucci 4, Palchamy Elango 4, Toru Takebayashi 5, Sei Harada 5, Miho Iida 5 and Madhav Thambisetty 1,*
Jackson A. Roberts 1, Vijay R. Varma 1, Chiung-Wei Huang 2, Yang An 2, Anup Oommen 3, Toshiko Tanaka 4, Luigi Ferrucci 4, Palchamy Elango 4, Toru Takebayashi 5, Sei Harada 5, Miho Iida 5 and Madhav Thambisetty 1,*
1
Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
2
Brain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
3
Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway H91-TK33, Ireland
4
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
5
Department of Preventive Medicine and Public Health, Keio University, Tokyo 160-8282, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1249; https://doi.org/10.3390/ijms21041249
Received: 19 December 2019 / Revised: 7 February 2020 / Accepted: 10 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue Metabolomics in Medicine)
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.
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Keywords:
metabolic syndrome; metabolomics; amino acids; fasting glucose; triglycerides; waist circumference; blood pressure
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MDPI and ACS Style
Roberts, J.A.; Varma, V.R.; Huang, C.-W.; An, Y.; Oommen, A.; Tanaka, T.; Ferrucci, L.; Elango, P.; Takebayashi, T.; Harada, S.; Iida, M.; Thambisetty, M. 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). Int. J. Mol. Sci. 2020, 21, 1249.
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