The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk
Open accessAbstract
Using an untargeted metabolomics approach in initial (N = 99 subjects) and replication cohorts (N = 1,162), we discovered and structurally identified a plasma metabolite associated with cardiovascular disease (CVD) risks, N6,N6,N6-trimethyl-L-lysine (trimethyllysine, TML). Stable-isotope-dilution tandem mass spectrometry analyses of an independent validation cohort (N = 2,140) confirmed TML levels are independently associated with incident (3-year) major adverse cardiovascular event risks (hazards ratio [HR], 2.4; 95% CI, 1.7-3.4) and incident (5-year) mortality risk (HR, 2.9; 95% CI, 2.0-4.2). Genome-wide association studies identified several suggestive loci for TML levels, but none reached genome-wide significance; and d9(trimethyl)-TML isotope tracer studies confirmed TML can serve as a nutrient precursor for gut microbiota-dependent generation of trimethylamine (TMA) and the atherogenic metabolite trimethylamine N-oxide (TMAO). Although TML was shown to be abundant in both plant- and animal-derived foods, mouse and human fecal cultures (omnivores and vegans) showed slow conversion of TML to TMA. Furthermore, unlike chronic dietary choline, TML supplementation in mice failed to elevate plasma TMAO or heighten thrombosis potential in vivo. Thus, TML is identified as a strong predictor of incident CVD risks in subjects and to serve as a dietary precursor for gut microbiota-dependent generation of TMAO; however, TML does not appear to be a major microbial source for TMAO generation in vivo.
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Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
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Self-citationHistone demethylation mediated by the nuclear amine oxidase homolog LSD1
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Self-citationMetabolomics enables precision medicine: “A White Paper, Community Perspective”
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Self-citationTransmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation
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Self-citationCarnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota
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Cited by
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Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051
Self-citationA Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors
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Self-citationIntestinal Microbiota in Cardiovascular Health and Disease
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Self-citationMicrobiota-derived metabolites as drivers of gut–brain communication
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Metadata
- Authors
- Li, X. S., Wang, Z., Cajka, T., Buffa, J. A., Nemet, I., Hurd, A. G., Gu, X., Skye, S. M., Roberts, A. B., Wu, Y., Li, L., Shahen, C. J., Wagner, M. A., Hartiala, J. A., Kerby, R. L., Romano, K. A., Han, Y., Obeid, S., Lüscher, T. F., Allayee, H., Rey, F. E., DiDonato, J. A., Fiehn, O., Tang, W. H. W., & Hazen, S. L.
- Venue
- JCI Insight
- Published
- 2018-03-22
- Volume
- 3
- Issue
- 6
- ISSN
- 2379-3708 (ISSN-L)
- OpenAlex
- W2790593817
- Cited by
- 167
- References
- 12
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- gold
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- Li, X. S., Wang, Z., Cajka, T., Buffa, J. A., Nemet, I., Hurd, A. G., Gu, X., Skye, S. M., Roberts, A. B., Wu, Y., Li, L., Shahen, C. J., Wagner, M. A., Hartiala, J. A., Kerby, R. L., Romano, K. A., Han, Y., Obeid, S., Lüscher, T. F., . . . Hazen, S. L. (2018). Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight. https://doi.org/10.1172/jci.insight.99096
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