The Impact of Obesity-Associated Glycine Deficiency on the Elimination of Endogenous and Exogenous Metabolites via the Glycine Conjugation Pathway

Authors

Hong Chang Tan
Jean W Hsu
E Shyong Tai
Shaji Chacko
Jean-Paul Kovalik
Farook Jahoor

Publication Date

1-1-2024

Journal

Frontiers in Endocrinology

DOI

10.3389/fendo.2024.1343738

PMID

38633754

PMCID

PMC11023637

PubMedCentral® Posted Date

4-3-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Bariatric Surgery, Benzoic Acid, Glycine, Hippurates, Obesity, Case-Control Studies, glycine deficiency, class III obesity, glycine conjugation, acylglycine, bariatric surgery

Abstract

BACKGROUND: Glycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised. However, it should be restored after bariatric surgery because of increased glycine production.

OBJECTIVE: 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.

METHODS: We recruited 21 participants with class III obesity and 21 with healthy weight as controls. At baseline, [1,2-

RESULTS: 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/m

CONCLUSION: 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.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04660513, identifier NCT04660513.