Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.
Children's Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, and Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States.
Front Endocrinol (Lausanne). 2024 Apr 3;15:1343738. doi: 10.3389/fendo.2024.1343738. eCollection 2024.
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.
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-C] 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 -value< 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/m). They had significantly lower plasma glycine concentration (168 ± 30 vs. 209 ± 50 μmol/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/m. Plasma glycine concentration increased from 164 ± 26 to 212 ± 38 μmol/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.
https://clinicaltrials.gov/study/NCT04660513, identifier NCT04660513.
甘氨酸是人体解毒系统的重要组成部分，因为它可以通过甘氨酸结合途径与潜在有毒的外源性和内源性产生的化合物和代谢物反应，从而通过尿液排出体外。由于肥胖个体的甘氨酸可用性降低，因此该解毒途径可能受损。然而，由于甘氨酸产量增加，在进行减肥手术后应该会恢复这种解毒途径。
检查与肥胖相关的甘氨酸缺乏对甘氨酸结合途径的影响。我们假设，来自内源性和外源性来源的酰基甘氨酸的合成速率在肥胖个体中显著降低，但在减肥手术后会增加。
我们招募了 21 名患有 III 类肥胖症的参与者和 21 名体重健康的对照组。在基线时，通过定量几种酰基甘氨酸的合成速率来输注 [1,2-C]甘氨酸，以研究甘氨酸结合途径。在减肥手术后的六个月，对肥胖参与者重复了相同的测量。数据以平均值 ±标准差表示，-值<0.05 被认为具有统计学意义。
首先比较了 20 名肥胖参与者的基线数据与对照组。与对照组相比，肥胖参与者的体重明显更重（平均 BMI 为 40.5 ± 7.1 与 20.8 ± 2.1 kg/m）。他们的血浆甘氨酸浓度明显较低（168 ± 30 与 209 ± 50 μmol/L），乙酰甘氨酸、异丁酰甘氨酸、tiglylglycine、异戊酰甘氨酸和己酰甘氨酸的绝对合成速率也较慢。肥胖参与者中有 16 名提供了术前和术后的数据。术后 BMI 从 40.9 ± 7.3 降至 31.6 ± 6.0 kg/m。血浆甘氨酸浓度从 164 ± 26 增加到 212 ± 38 μmol/L），并与乙酰甘氨酸、异丁酰甘氨酸、tiglylglycine、异戊酰甘氨酸和己酰甘氨酸的排泄率显著升高相关。苯甲酸（一种外源性二羧酸）作为苯甲酰甘氨酸排泄；肥胖参与者的合成速率明显较慢，但减肥手术后增加。
与肥胖相关的甘氨酸缺乏会损害人体通过甘氨酸结合途径消除内源性和外源性代谢物/化合物的能力。减肥手术后，当甘氨酸供应恢复时，这种损伤会得到改善。这些发现意味着由于线粒体内有毒代谢物的积累，饮食中补充甘氨酸可能会治疗与肥胖相关的代谢并发症。
https://clinicaltrials.gov/study/NCT04660513，标识符 NCT04660513。
