Dan Nguyen1, Jean W Hsu, Farook Jahoor, Rajagopal V Sekhar. 1. Translational Metabolism Unit (D.N., R.V.S.), Division of Diabetes, Endocrinology, and Metabolism; Diabetes and Endocrinology Research Center (D.N., R.V.S.); and Department of Medicine (J.W.H., F.J.), U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Abstract
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.
BACKGROUND:HIV-infectedpatients 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-infectedpatients, 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-infectedpatients: 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-infectedpatients warrants further investigation.
Authors: Helena S Vassimon; Rafael Deminice; Alcyone A Machado; Jacqueline P Monteiro; Alceu Afonso Jordao Journal: Curr HIV Res Date: 2010-07 Impact factor: 1.581
Authors: R Mastrocola; F Restivo; I Vercellinatto; O Danni; E Brignardello; M Aragno; G Boccuzzi Journal: J Endocrinol Date: 2005-10 Impact factor: 4.286
Authors: F J Palella; K M Delaney; A C Moorman; M O Loveless; J Fuhrer; G A Satten; D J Aschman; S D Holmberg Journal: N Engl J Med Date: 1998-03-26 Impact factor: 91.245
Authors: Guenther Boden; Carol Homko; Carlos A Barrero; T Peter Stein; Xinhua Chen; Peter Cheung; Chiara Fecchio; Sarah Koller; Salim Merali Journal: Sci Transl Med Date: 2015-09-09 Impact factor: 17.956
Authors: John P Richie; Sailendra Nichenametla; Wanda Neidig; Ana Calcagnotto; Jeremy S Haley; Todd D Schell; Joshua E Muscat Journal: Eur J Nutr Date: 2014-05-05 Impact factor: 5.614
Authors: Thomas R Ziegler; Suzanne E Judd; Joshua H Ruff; Grace A McComsey; Allison Ross Eckard Journal: AIDS Res Hum Retroviruses Date: 2017-02-27 Impact factor: 2.205
Authors: Roberto Carlos Burini; Maria Doroteia Borges-Santos; Fernando Moreto; Yong- Ming Yu Journal: Amino Acids Date: 2018-02-01 Impact factor: 3.520