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Emerging Perspectives on Essential Amino Acid Metabolism in Obesity and the Insulin-Resistant State
Open accessAbstract
Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives, in particular BCAA, sulfur amino acids, tyrosine, and phenylalanine, are apparent with obesity and insulin resistance, often before the onset of clinically diagnosed T2DM. This review provides an overview of these changes and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+).
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“BCAAs have recently been demonstrated to accumulate in the context of obesity and insulin resistance (Adams, 2011; Newgard et al., 2009; Wang et al., 2011), though the mechanisms leading to this metabolic phenotype (i.e., higher intake, decreased catabolism) are not yet clear.”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Adams, 2011
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“Mpc inhibition may potentiate oxidation of BCAAs or other amino acids that accumulate in the context of insulin resistance (Adams, 2011; Newgard et al., 2009; Wang et al., 2011).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Adams, 2011
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Dong, Q., Sidra, S., Gieger, C., Wang‐Sattler, R., Rathmann, W., Prehn, C. P., Adamski, J., Köenig, W., Peters, A., Grallert, H., et al. (2023) · Metabolites · doi:10.3390/metabo13020227 · Cited by 28
Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model
Piccolo, B. D., Graham, J. L., Stanhope, K. L., Fiehn, O., Havel, P. J., & Adams, S. H. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00052.2016 · Cited by 27
CE‐MS‐based serum fingerprinting to track evolution of type 2 diabetes mellitus
Ciborowski, M., Adamska-Patruno, E., Rusak, M., Godzień, J., Wilk, J., Citko, A., Bauer, W., Górska, M., & Kretowski, A. J. (2015) · Electrophoresis · doi:10.1002/elps.201500021 · Cited by 26
Identification of Insulin Resistance Biomarkers in Metabolic Syndrome Detected by UHPLC-ESI-QTOF-MS
Alsoud, L. O., Soares, N. C., Al-Hroub, H. M., Mousa, M., Kasabri, V. N., Bulatova, N., Suyagh, M. F., Alzoubi, K. H., El‐Huneidi, W., Abu‐Irmaileh, B., et al. (2022) · Metabolites · doi:10.3390/metabo12060508 · Cited by 26
Hotea, I., Sîrbu, C. B., Plotuna, A.-M., Tîrziu, E., Badea, C., Berbecea, A. A., Dragomirescu, M., & Radulov, I. (2023) · Metabolites · doi:10.3390/metabo13070800 · Cited by 26
Sansbury, B. E., Bhatnagar, A., & Hill, B. G. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00453 · Cited by 24
Gordon-Dseagu, V., Derkach, A., Xiao, Q., Williams, I., Sampson, J. N., & Stolzenberg‐Solomon, R. Z. (2019) · Metabolomics · doi:10.1007/s11306-019-1472-y · Cited by 24
Regulation of hepatic branched-chain α-ketoacid dehydrogenase complex in rats fed a high-fat diet
Kadota, Y., Toyoda, T., Kitaura, Y., Adams, S. H., & Shimomura, Y. (2013) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2013.07.003 · Cited by 26
Elshorbagy, A. K., Samocha‐Bonet, D., Jernerén, F., Turner, C., Refsum, H., & Heilbronn, L. K. (2018) · Journal of Nutrition · doi:10.1093/jn/nxy062 · Cited by 25
Vanweert, F., Boone, S. C., Brouwers, B., Mook-Kanamori, D. O., de Mutsert, R., Rosendaal, F. R., Lamb, H. J., Schrauwen‐Hinderling, V. B., Schrauwen, P., Hesselink, M. K. C., et al. (2021) · International Journal of Obesity · doi:10.1038/s41366-021-00815-4 · Cited by 24
Everman, S., Mandarino, L. J., Carroll, C. C., & Katsanos, C. S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120049 · Cited by 25
Amino Acid-Related Metabolic Signature in Obese Children and Adolescents
Polidori, N., Grasso, E. A., Chiarelli, F., & Giannini, C. (2022) · Nutrients · doi:10.3390/nu14071454 · Cited by 29
Mahbub, M., Yamaguchi, N., Takahashi, H., Hase, R., Ishimaru, Y., Sunagawa, H., Amano, H., Kobayashi‐Miura, M., Kanda, H., Fujita, Y., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17710-6 · Cited by 24
Oluwagbemigun, K., Anesi, A., Ulaszewska, M., Clarke, G. A., Alexy, U., Schmid, M. C., Roden, M., Herder, C., Mattivi, F., & Nöthlings, U. (2020) · Scientific Reports · doi:10.1038/s41598-020-63313-z · Cited by 24
Tan, H. C., Hsu, J. W.-C., Kovalik, J., Eng, A. K. H., Chan, W. H., Khoo, C. M., Tai, E. S., Chacko, S. K., & Jahoor, F. (2020) · Journal of Nutrition · doi:10.1093/jn/nxaa298 · Cited by 25
Mosher, J., Zhang, W., Blumhagen, R. Z., D’Alessandro, A., Nemkov, T. G., Hansen, K. C., Hesselberth, J. R., & Reis, T. (2015) · Developmental Biology · doi:10.1016/j.ydbio.2015.07.021 · Cited by 23
Polakof, S., Rémond, D., Bernalier‐Donadille, A., Rambeau, M., Pujos‐Guillot, E., Comte, B., Dardevet, D. P., & Savary‐Auzeloux, I. (2016) · European Journal of Nutrition · doi:10.1007/s00394-016-1302-1 · Cited by 22
BCKA down-regulates mTORC2-Akt signal and enhances apoptosis susceptibility in cardiomyocytes
Guo, X., Huang, C., Lian, K., Wang, S., Zhao, H., Yan, F., Zhang, X., Zhang, J., Xie, H., An, R. F., et al. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.09.162 · Cited by 21
Metadata
- Authors
- Adams, S. H.
- Affiliations
- Agricultural Research Service (US)
- Corresponding author
- Adams, Sean H.
- ORCID
- Adams, Sean H.
- Venue
- Advances in Nutrition
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 2
- Issue
- 6
- Pages
- 445-456
- ISSN
- 2156-5376 (ISSN-L)
- 2161-8313
- PMC
- PMC3226382
- OpenAlex
- W1995187187
- Cited by
- 394
- References
- 143
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 27 · 2023: 22 · 2022: 31 · 2021: 28 · 2020: 21 · 2019: 29 · 2018: 22 · 2017: 34 · 2016: 27 · 2015: 34 · 2014: 44 · 2013: 22 · 2012: 12
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Advances in Nutrition (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Agriculture (5306‐51530‐019‐00, 5306‐51530‐019)
- National Institutes of Health
- Agricultural Research Service (5306‐51530‐019‐00)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078328-02S, R01DK078328)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- obesity, insulin resistance, type 2 diabetes, prediabetes, branched-chain amino acids, sulfur-containing amino acids, methionine oxidation, redox homeostasis, free fatty acids, metabolomics, impaired glucose tolerance
- MeSH terms
- Amino Acids, Sulfur, Transaminases, Animals, Cysteine, Cystine, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Methionine, Models, Biological, Obesity, Oxidation-Reduction, Phenylalanine, Tyrosine, Oxidative Stress, Amino Acids, Aromatic, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
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