WEPE091 - Poster Exhibition
Reduced skeletal muscle mitochondrial function in older HIV-positive men is associated with low aerobic exercise capacity
H. Ortmeyer1,2, A. Ryan1,2, C. Hafer-Macko2,3, K. Oursler1,2
1University of Maryland School of Medicine, Medicine, Baltimore, United States, 2Baltimore Veterans Affairs Medical Center, Geriatric Research, Education, and Clinical Center, Baltimore, United States, 3University of Maryland School of Medicine, Neurology, Baltimore, United States
Background: We previously reported a 40% reduction in aerobic capacity in older (50+ years) HIV-infected men. Impaired skeletal muscle oxidative function is a determinant of poor aerobic capacity, but can improve with exercise training. The objective of this study was to compare skeletal muscle mitochondrial enzyme activity between older HIV-infected and negative men, and determine the relationship to aerobic capacity.
Methods: This cross-sectional study included 10 HIV-infected men on NRTI-based therapy with either protease inhibitors (n=7) or efavirenz (n=3) and eight age and BMI-matched HIV negative men. We measured aerobic capacity (peakVO2) and body composition (DXA, CT). Skeletal muscle samples were collected by needle biopsy of the vastus lateralis. Enzyme activity assays for mitochondrial function including fatty acid oxidation (acyl-CoA synthase, carnitine palmitoyltransferase, and ß-hydroxyacyl CoA dehydrogenase [ß-HAD]), oxidation (citrate synthase [CS]), and oxidative phosphorylation (electron transport chain [ETC] complexes I,II,IV, and V) were performed in muscle homogenates prepared from lyophilized microdissected muscle.
Results: Age (mean 55 years), BMI (mean 28 kg/m2), total lean mass and mid-thigh muscle area were similar between groups (p>0.1). HIV-infected men had lower total fat mass and visceral adipose tissue (p≤0.05). PeakVO2 was 33% lower in HIV-infected men compared to HIV negative men (mean ±SE; 25 ±3 vs. 33 ±1 mL/kg/min, p< 0.01). β-HAD and CS activity (µmol/min/mg protein) were significantly lower in HIV-infected men compared to HIV negative men (Figure 1) and correlated significantly with peakVO2 (Figure 2). There were no differences in ETC enzyme activities between the two groups.
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Conclusions: Older HIV-infected men on modern therapy have intact ETC skeletal muscle enzyme activity, but reduced oxidative enzyme activity, which is significantly associated with low aerobic capacity. These findings support the possibility that exercise training will increase aerobic capacity and improve mitochondrial oxidative function in older HIV-infected adults, comparable to changes seen with exercise in HIV negative adults.
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