Effect of Increasing Glutathione With Cysteine and Glycine Supplementation on Mitochondrial Fuel Oxidation, Insulin Sensitivity, and Body Composition in Older HIV-Infected Patients

被引:64
作者
Dan Nguyen [1 ,2 ]
Hsu, Jean W. [3 ]
Jahoor, Farook [3 ]
Sekhar, Rajagopal V. [1 ,2 ]
机构
[1] Baylor Coll Med, Div Diabet Endocrinol & Metab, Translat Metab Unit, USDA,ARS,Childrens Nutr Res Ctr,Dept Pediat, Houston, TX 77030 USA
[2] Baylor Coll Med, Diabet & Endocrinol Res Ctr, Childrens Nutr Res Ctr, USDA,ARS,Dept Pediat, Houston, TX 77030 USA
[3] Baylor Coll Med, ARS, USDA, Childrens Nutr Res Ctr,Dept Pediat,Dept Med, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
METABOLIC FLEXIBILITY; SUBSTRATE OXIDATION; DNA-DAMAGE; RESISTANCE; LIPODYSTROPHY; STRESS; MECHANISMS; INDUCTION; MUSCLE;
D O I
10.1210/jc.2013-2376
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: HIV-infected patients are reported to have impaired oxidation of fatty acids despite increased availability, suggesting a mitochondrial defect. We investigated whether diminished levels of a key mitochondrial antioxidant, glutathione (GSH), was contributing to defective fatty acid oxidation in older HIV-infected patients, and if so, the metabolic mechanisms contributing to GSH deficiency in these patients. Methods: In an open-label design, 8 older GSH-deficient HIV-infected males were studied before and after 14 days of oral supplementation with the GSH precursors cysteine and glycine. A combination of stable-isotope tracers, calorimetry, hyperinsulinemic-euglycemic clamp, and dynamometry were used to measure GSH synthesis, fasted and insulin-stimulated (fed) mitochondrial fuel oxidation, insulin sensitivity, body composition, anthropometry, forearm-muscle strength, and lipid profiles. Results: Impaired synthesis contributed to GSH deficiency in the patients and was restored with cysteine plus glycine supplementation. GSH improvement was accompanied by marked improvements in fasted and fed mitochondrial fuel oxidation. Associated benefits included improvements in insulin sensitivity, body composition, anthropometry, muscle strength, and dyslipidemia. Conclusions: This work identifies 2 novel findings in older HIV-infected patients: 1) diminished synthesis due to decreased availability of cysteine and glycine contributes to GSH deficiency and can be rapidly corrected by dietary supplementation of these precursors and 2) correction of GSH deficiency is associated with improvement of mitochondrial fat and carbohydrate oxidation in both fasted and fed states and with improvements in insulin sensitivity, body composition, and muscle strength. The role of GSH on ameliorating metabolic complications in older HIV-infected patients warrants further investigation.
引用
收藏
页码:169 / 177
页数:9
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