De novo glycine synthesis is reduced in adults with morbid obesity and increases following bariatric surgery

Authors: TAN, HONG - Singapore General Hospital; HSU, JEAN - Children'S Nutrition Research Center (CNRC); TAI, E SHYONG - National University Hospital Singapore; CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC); WU, VIEON - Singapore General Hospital; LEE, CHUN - Duke-Nus Medical School; KOVALIK, JEAN-PAUL - Duke-Nus Medical School; JAHOOR, FAROOK - Children'S Nutrition Research Center (CNRC)

Submitted to: Frontiers in Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2022
Publication Date: 6/9/2022
Citation: Tan, H.C., Hsu, J.W., Tai, E., Chacko, S., Wu, V., Lee, C.F., Kovalik, J., Jahoor, F. 2022. De novo glycine synthesis is reduced in adults with morbid obesity and increases following bariatric surgery. Frontiers in Endocrinology. 9(13). Article 900343. https://doi.org/10.3389/fendo.2022.900343.
DOI: https://doi.org/10.3389/fendo.2022.900343

Interpretive Summary: Insulin resistance is a condition when cells in muscles, fat, and liver do not respond efficiently to insulin and are unable to easily take up glucose from circulation. Obesity is a risk factor for insulin resistance and is associated with disturbances in the metabolism of not only glucose and lipids, but also of certain amino acids. Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the mechanism responsible for this reduced glycine concentration remains unclear. Scientists in Houston, Texas demonstrated that low plasma glycine concentration in morbidly obese condition in humans is associated with impaired glycine synthesis and this is improved after bariatric surgery. This finding implies that glycine can be regarded as a conditionally essential amino acid in obesity, and that plasma glycine concentration can be raised by simple measures such as dietary supplementation.

Technical Abstract: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance. Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI >/- 32.5 kg/m2) to those with healthy weight (BMI < 25 kg/m2), and 2) Comparing glycine kinetic changes in participants with morbid obesity after bariatric surgery. [1,2-13C2] glycine, [2,3,3-2H3] serine, and [2H5] phenylalanine were infused to compare the glycine kinetic parameters between 21 participants with morbid obesity and 21 controls with healthy weight. Participants with morbid obesity then underwent bariatric surgery and 17 were re-studied 6 months later. Data were analyzed by non-parametric methods and presented as median (interquartile range). Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced de novo glycine synthesis rate at 86.2 (64.5-111) vs.124 (103-159) µmol·kg LBM-1xh1, p < 0.001. Following surgery, body weight and insulin resistance decreased, and this was accompanied by significant increases in plasma glycine concentration to 210 (191-243) µmol/L as well as the de novo glycine synthesis rate to 127 (98.3-133) µmol·kg LBM-1·h-1, p < 0.001 vs. baseline. Hypoglycinemia in participants with morbid obesity was associated with impaired de novo glycine synthesis. The increase in plasma glycine concentration and de novo glycine synthesis plus the marked improvement in insulin resistance after bariatric surgery suggest that hypoglycinemia may be secondary to impaired glycine synthesis because of obesity-induced insulin resistance.