Reducing plasma HIV RNA improves muscle amino acid metabolism - PubMed (original) (raw)

Reducing plasma HIV RNA improves muscle amino acid metabolism

Kevin E Yarasheski et al. Am J Physiol Endocrinol Metab. 2005 Jan.

Abstract

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 (Ra Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (> or =1 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 (CD4 = 0-311 cells/microl; HIV RNA = 10-375 x 10(3) copies/ml). We utilized stable isotope tracer methodologies ([13C]Leu and [15N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma Ra 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/microl, 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), Ra Gln decreased (387 +/- 33 vs. 323 +/- 15 micromol.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, approximately 3 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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Figures

Fig. 1

Fig. 1

Mixed muscle protein synthesis rate was increased when plasma human immunodeficiency virus (HIV) RNA was reduced (*P = 0.01). Symbols represent individual subjects. Muscle protein synthesis expressed as a fraction of whole body protein synthesis (Table 4) was 12 ± 2% when HIV RNA was high and 15 ± 2% when HIV RNA was lower (P = 0.01), but still lower than 24–25% in seronegative control subjects (44).

Fig. 2

Fig. 2

Plasma glutamine (Gln) rate of appearance was reduced when plasma HIV RNA was reduced (*P = 0.04). FFM, fat-free mass. Symbols represent individual subjects.

Fig. 3

Fig. 3

Muscle chymotrypsin-like activity was reduced when plasma HIV RNA was reduced (*P = 0.03), whereas the catalytic activity of other enzymes present in the 20S proteasome core [trypsin-like, peptidyl glutamyl peptide hydrolase (PGPH)] was not affected.

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