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Pediatrics

Preliminary evidence of glycine as a biomarker of cardiovascular disease risk in children with obesity

International Journal of Obesity volume 47, pages 1023–1026 (2023)Cite this article

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Abstract

Glycine (GLY) is a substrate for a wide range of metabolic processes. Several preclinical and adult studies demonstrated inverse associations of GLY with obesity, cardiovascular disease (CVD) and diabetes. However, little evidence is available on relationships between GLY and CVD risk in children. We assessed links between circulating GLY and biomarkers of CVD in children with obesity. Participants included both male and females with normal weight (NW, n = 6) and obesity (OB, n = 15), with age 14–18 years and Tanner stage >IV. Concentrations of GLY, branched chain amino acids (BCAA), and 25-hydroxy vitamin-D [25(OH)D], glucose, insulin, adiponectin, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured using established techniques, and body composition by DXA. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Our study identified major relationships of GLY (p-value < 0.01 for all) of GLY with visceral fat (r2 = 0.40), BCAA (r2 = 0.44), HOMA-IR (r2 = 0.33), 25(OH)D (r2 = 0.48), IL-6 (r2 = 0.46) and adiponectin (r2 = 0.39). Given that CVD progression is a continuum and the disease itself is not present in children and biomarkers are typically used to monitor CVD in children, the links between GLY and biomarkers of CVD provide evidence for the first time of a potential role for GLY in CVD in children with obesity.

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Fig. 1: Relationship of glycine (GLY) with novel biomarkers of CVD.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. White PJ, Lapworth AL, McGarrah RW, Kwee LC, Crown SB, Ilkayeva O, et al. Muscle-liver trafficking of BCAA-derived nitrogen underlies obesity-related glycine depletion. Cell Rep. 2020;33:108375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tan HC, Hsu JW, Tai ES, Chacko S, Wu V, Lee CF, et al. De novo glycine synthesis is reduced in adults with morbid obesity and increases following bariatric surgery. Front Endocrinol. 2022;13:900343.

    Article  Google Scholar 

  3. Alves A, Bassot A, Bulteau AL, Pirola L, Morio B. Glycine metabolism and its alterations in obesity and metabolic diseases. Nutrients. 2019;11:1356.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sekhar RV, McKay SV, Patel SG, Guthikonda AP, Reddy VT, Balasubramanyam A, et al. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care. 2011;34:162–7.

    Article  CAS  PubMed  Google Scholar 

  5. Rom O, Liu Y, Liu Z, Zhao Y, Wu J, Ghrayeb A, et al. Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome. Sci Transl Med. 2020;12:eaaz2841.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ruiz-Ramírez A, Ortiz-Balderas E, Cardozo-Saldaña G, Diaz-Diaz E, El-Hafidi M. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clin Sci (London, England: 1979). 2014;126:19–29.

    Article  Google Scholar 

  7. Takashina C, Tsujino I, Watanabe T, Sakaue S, Ikeda D, Yamada A, et al. Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance. Nutr Metab (Lond). 2016;13:5.

    Article  PubMed  Google Scholar 

  8. Imenshahidi M, Hossenzadeh H. Effects of glycine on metabolic syndrome components: a review. J Endocrinol Investig. 2022;45:927–39.

    Article  CAS  Google Scholar 

  9. Glynn EL, Piner LW, Huffman KM, Slentz CA, Elliot-Penry L, AbouAssi H, et al. Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans. Diabetologia. 2015;58:2324–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Adeva-Andany M, Souto-Adeva G, Ameneiros-Rodríguez E, Fernández-Fernández C, Donapetry-García C, Domínguez-Montero A. Insulin resistance and glycine metabolism in humans. Amino Acids. 2018;50:11–27.

    Article  CAS  PubMed  Google Scholar 

  11. Thalacker-Mercer AE, Ingram KH, Guo F, Ilkayeva O, Newgard CB, Garvey WTBMI. RQ, diabetes, and sex affect the relationships between amino acids and clamp measures of insulin action in humans. Diabetes. 2014;63:791–800.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ding Y, Svingen GF, Pedersen ER, Gregory JF, Ueland PM, Tell GS, et al. Plasma glycine and risk of acute myocardial infarction in patients with suspected stable angina pectoris. J Am Heart Assoc. 2015;5:e002621.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Venkatesh R, Srinivasan K, Singh SA. Effect of arginine:lysine and glycine:methionine intake ratios on dyslipidemia and selected biomarkers implicated in cardiovascular disease: a study with hypercholesterolemic rats. Biomed Pharmacother Biomed Pharmacother. 2017;91:408–14.

    Article  CAS  PubMed  Google Scholar 

  14. El Hafidi M, Pérez I, Zamora J, Soto V, Carvajal-Sandoval G, Baños G. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. Am J Physiol Regul Integr Comparat Physiol. 2004;287:R1387–93.

    Article  CAS  Google Scholar 

  15. Cosentino RG, Churilla JR, Josephson S, Molle-Rios Z, Hossain MJ, Prado W, et al. Branched chain amino acid-inflammation relationship in youth with obesity: a randomized controlled intervention study. J Clin Endocrinol Metab. 2021;106:3129–39.

    Article  PubMed  Google Scholar 

  16. Short KR, Chadwick JQ, Teague AM, Tullier MA, Wolbert L, Coleman C, et al. Effect of obesity and exercise training on plasma amino acids and amino metabolites in American Indian adolescents. J Clin Endocrinol Metab. 2019;104:3249–61.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Polidori N, Grasso EA, Chiarelli F, Giannini C. Amino acid-related metabolic signature in obese children and adolescents. Nutrients. 2022;14:1454.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17:448–53.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9:311–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hossain MJ, Levinson A, George D, Canas J, Kumar S, Balagopal PB. Vitamin D status and cardiovascular risk in obesity: effect of physical activity in nonvitamin D supplemented adolescents. Metab Syndrome Related Disord. 2018;16:197–203.

    Article  CAS  Google Scholar 

  21. Kim D, Howard AG, Blanco E, Burrows R, Correa-Burrows P, Memili A, et al. Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: the Santiago longitudinal study. Nutr Metab Cardiovasc Dis: NMCD. 2022;32:1055–63.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the volunteers for their participation; Linda Russell, and Leslie Berry for excellent support in coordinating the study; Burnese Rutledge, Shiela Smith, and the nursing staff of the Clinical Research Center at the Wolfson Children’s Hospital for their superb clinical assistance; Karl Mann, Shawn Sweeten, Brian Dughi, Brenda Sager, Lynda Everline, and Astride Altomare (Nemours Biomedical Analysis Laboratory) for their skilled technical assistance. This work was partly supported by the following funding agencies: American Heart Association#0030343B; American Diabetes Association#1-14-CE-04; Nemours Biomedical Research# none.

Funding

This work was partly supported by the following funding agencies: American Heart Association#0030343B; American Diabetes Association#1-14-CE-04; Nemours Biomedical Research -no number.

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Authors and Affiliations

  1. California State University – San Bernardino, San Bernardino, CA, USA

    Wagner Luiz do Prado

  2. Biomedical Research, Nemours Children’s Health System, Jacksonville, FL, USA

    Samantha Josephson & P. Babu Balagopal

  3. Department of Kinesiology, University of North Florida, Jacksonville, FL, USA

    Ralph G. Cosentino & James R. Churilla

  4. Department of Biostatistics, Nemours Children’s Health System, Wilmington, DE, USA

    Jobayer Hossain

  5. Department of Pediatrics, Mayo Clinic College of Medicine, Rochester, MN, USA

    P. Babu Balagopal

Authors
  1. Wagner Luiz do Prado
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  2. Samantha Josephson
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  3. Ralph G. Cosentino
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  4. James R. Churilla
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  5. Jobayer Hossain
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  6. P. Babu Balagopal
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Contributions

WLP: extracting and analyzing data, interpreting results, updating reference lists and creating tables and figures and manuscript drafting; SJ: extracting and analyzing data, data organization, creating tables and figures and manuscript drafting; RGC: data organization, interpreting results, updating reference lists and manuscript drafting; JRC: interpreting results, and critical review and manuscript editing; MJH: statistical analyses, critical review and manuscript editing; PBB: study design, data analysis, interpretation of the data, writing of the manuscript, critical review and finalizing the manuscript; all authors read and approved the final draft of the manuscript.

Corresponding author

Correspondence to P. Babu Balagopal.

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Competing interests

No financial conflict of interest. Part of the results on glycine have been previously published [Cosentino RG, et al. Branched-chain Amino Acids and Relationship with Inflammation in Youth With Obesity: A Randomized Controlled Intervention Study. J Clin Endocrinol Metab. 2021; 106(11):3129–3139] and in abstract form at The Obesity Week (The Obesity Society Annual Meeting) 2021 [Prado WL, et al. Effect of Obesity and Physical Activity on Circulating Concentrations of Glycine in Adolescents].

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do Prado, W.L., Josephson, S., Cosentino, R.G. et al. Preliminary evidence of glycine as a biomarker of cardiovascular disease risk in children with obesity. Int J Obes 47, 1023–1026 (2023). https://doi.org/10.1038/s41366-023-01354-w

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