The impact of obesity-associated glycine deficiency on the elimination of endogenous and exogenous metabolites via the glycine conjugation pathway

Authors: TANG, HONG CHAN - 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); 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: 3/15/2024
Publication Date: 4/3/2024
Citation: Tang, H., Hsu, J.W., Tai, E., Chacko, S., Kovalik, J., Jahoor, F. 2024. The impact of obesity-associated glycine deficiency on the elimination of endogenous and exogenous metabolites via the glycine conjugation pathway. Frontiers in Endocrinology. 15:Article 1343738. https://doi.org/10.3389/fendo.2024.1343738.
DOI: https://doi.org/10.3389/fendo.2024.1343738

Interpretive Summary: Glycine is an amino acid that is central to human metabolism and is required in large amounts by the human body. Plasma glycine concentration is low in morbidly obese condition in humans and is associated with impaired glycine synthesis, and this is improved after bariatric surgery. Glycine is an integral component of the human detoxification system. The objective of this study was to examine the impact of obesity-associated glycine deficiency and bariatric surgery on detoxification system in humans. Scientists in Houston, Texas demonstrated that obesity-associated glycine deficiency impairs the human detoxification system, and this impairment is improved when glycine supply is restored after bariatric surgery. This finding implies that dietary glycine supplementation could treat obesity-associated metabolic complications due to the accumulation of toxic metabolites by helping the body get rid of harmful substances more efficiently.

Technical Abstract: To examine the impact of obesity-associated glycine deficiency on the glycine conjugation pathway. We hypothesize that the synthesis rates of acylglycines from endogenous and exogenous sources are significantly reduced in individuals with obesity but increase after bariatric surgery. We recruited 21 participants with class III obesity and 21 with healthy weight as controls. At baseline, [1,2-13C2] glycine was infused to study the glycine conjugation pathway by quantifying the synthesis rates of several acylglycines. The same measurements were repeated in participants with obesity six months after bariatric surgery. Data are presented as mean ± standard deviation, and pvalue<0.05 is considered statistically significant. Baseline data of 20 participants with obesity were first compared to controls. Participants with obesity were significantly heavier than controls (mean BMI 40.5 +/- 7.1 vs. 20.8 +/- 2.1 kg/m2). They had significantly lower plasma glycine concentration (168 +/- 30 vs. 209 +/- 50 mmol/L) and slower absolute synthesis rates of acetylglycine, isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. Pre- and post-surgery data were available for 16 participants with obesity. Post-surgery BMI decreased from 40.9 +/- 7.3 to 31.6 +/- 6.0 kg/m2. Plasma glycine concentration increased from 164 +/- 26 to 212 +/- 38 mmol/L) and was associated with significantly higher rates of excretion of acetylglycine, isobutyrylglycine, tigylglycine,isovalerylglycine, and hexanoylglycine. Benzoic acid (a xenobiotic dicarboxylic acid) is excreted as benzoylglycine; its synthesis rate was significantly slower in participants with obesity but increased after bariatric surgery. Obesity-associated glycine deficiency impairs the human body’s ability to eliminate endogenous and exogenous metabolites/compounds via the glycine conjugation pathway. This impairment is ameliorated when glycine supply is restored after bariatric surgery. These findings imply that dietary glycine supplementation could treat obesity-associated metabolic complications due to the accumulation of intramitochondrial toxic metabolites.