Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 288, Issue 1, Pages E278-E284Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00359.2004
Keywords
human immunodeficiency virus; metabolic complications; body composition; mass spectrometry; antiretroviral medications; cachexia; lentivirus
Categories
Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000036, P41RR000954] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI025903] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK054163, R01DK049393, R01DK059531, R56DK049393, P30DK056341] Funding Source: NIH RePORTER
- NCRR NIH HHS [P41 RR000954, M01 RR000036, RR-00954, RR-00036] Funding Source: Medline
- NIAID NIH HHS [U01 AI025903, AI-25903] Funding Source: Medline
- NIDDK NIH HHS [R01 DK054163, P30 DK056341, DK-54163, DK-49393, R01 DK054163-02, R56 DK049393, DK-56341, R01 DK049393, R01 DK054163-05, R01 DK059531, R01 DK054163-03, R01 DK054163-04, DK-59531] Funding Source: Medline
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We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577-E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (R-a Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (greater than or equal to1 log) increased muscle protein synthesis rate and reduced R-a Gln and muscle proteasome activity in 10 men and 1 woman (22-57 yr, 60-108 kg, 17-33 kg muscle) with advanced HIV (CD=0-311 cells/mul; HIV RNA=10-375x10(3) copies/ml). We utilized stable isotope tracer methodologies ([C-13] Leu and [N-15] Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma R-a Gln in these subjects before and 4 mo after initiating their first or a salvage antiretroviral therapy regimen. After treatment, median CD4 increased (98 vs. 139 cells/mul, P=0.009) and median HIV RNA was reduced (155,828 vs. 100 copies/ml, P=0.003). Mixed muscle protein synthesis rate increased (0.062+/-0.005 vs. 0.078+/-0.006%/h, P=0.01), R-a Gln decreased (387+/-33 vs. 323+/-15 mumol.kg fat-free mass(-1).h(-1), P=0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% (P=0.03). Muscle mass was only modestly increased (1 kg, P=not significant). We estimated that, for each 10,000 copies/ml reduction in HIV RNA, similar to3 g of additional muscle protein are synthesized per day. These findings suggest that reducing HIV RNA increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein synthesis relative to whole body protein synthesis rate is not restored to normal, so muscle mass is not substantially increased.
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