The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Metabolite Profiling Identifies Pathways Associated With Metabolic Risk in Humans
Open accessAbstract
Background—: Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood. Methods and Results—: To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmö Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, −0.04 to −0.22 per 1-SD change in log-glutamine; P <0.001), glutamate (0.05 to 0.14; P <0.001), and the glutamine-to-glutamate ratio (−0.05 to −0.20; P <0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-to-glutamate ratio was associated with lower risk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted P =0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance ( P =0.01) and decreased blood pressure ( P <0.05). Conclusions—: Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice.
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Metabolite profiles and the risk of developing diabetes
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AN INVESTIGATION OF CORONARY HEART DISEASE IN FAMILIES
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Cited by
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021
Branched-chain amino acids in metabolic signalling and insulin resistance
Lynch, C. J., & Adams, S. H. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.171 · Cited by 1,461
Novel biomarkers for pre-diabetes identified by metabolomics
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Metadata
- Authors
- Cheng, S., Rhee, E. P., Larson, M. G., Lewis, G. D., McCabe, E. L., Shen, D., Palma, M. J., Roberts, L. D., Dejam, A., Souza, A. L., Deik, A. A., Magnusson, M., Fox, C. S., O'Donnell, C. J., Vasan, R. S., Melander, O., Clish, C. B., Gerszten, R. E., & Wang, T. J.
- Venue
- Circulation
- Published
- 2012-05-08
- Volume
- 125
- Issue
- 18
- Pages
- 2222-2231
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2144636739
- Cited by
- 587
- References
- 43
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Cheng, S., Rhee, E. P., Larson, M. G., Lewis, G. D., McCabe, E. L., Shen, D., Palma, M. J., Roberts, L. D., Dejam, A., Souza, A. L., Deik, A. A., Magnusson, M., Fox, C. S., O'Donnell, C. J., Vasan, R. S., Melander, O., Clish, C. B., Gerszten, R. E., & Wang, T. J. (2012). Metabolite Profiling Identifies Pathways Associated With Metabolic Risk in Humans. Circulation. https://doi.org/10.1161/circulationaha.111.067827
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