Skeletal muscle cellular metabolism in older HIV-infected men

Physiol Rep. 2016 May;4(9):e12794. doi: 10.14814/phy2.12794.

Abstract

Skeletal muscle mitochondrial dysfunction may contribute to low aerobic capacity. We previously reported 40% lower aerobic capacity in HIV-infected men compared to noninfected age-matched men. The objective of this study was to compare skeletal muscle mitochondrial enzyme activities in HIV-infected men on antiretroviral therapy (55 ± 1 years of age, n = 10 African American men) with age-matched controls (55 ± 1 years of age, n = 8 Caucasian men), and determine their relationship with aerobic capacity. Activity assays for mitochondrial function including enzymes involved in fatty acid activation and oxidation, and oxidative phosphorylation, were performed in homogenates prepared from vastus lateralis muscle. Hydrogen peroxide (H2O2), cardiolipin, and oxidized cardiolipin were also measured. β-hydroxy acyl-CoA dehydrogenase (β-HAD) (38%) and citrate synthase (77%) activities were significantly lower, and H2O2 (1.4-fold) and oxidized cardiolipin (1.8-fold) were significantly higher in HIV-infected men. VO2peak (mL/kg FFM/min) was 33% lower in HIV-infected men and was directly related to β-HAD and citrate synthase activity and inversely related to H2O2 and oxidized cardiolipin. Older HIV-infected men have reduced oxidative enzyme activity and increased oxidative stress compared to age-matched controls. Further research is crucial to determine whether an increase in aerobic capacity by exercise training will be sufficient to restore mitochondrial function in older HIV-infected individuals.

Keywords: Cardiolipin; citrate synthase; glycogen synthase; hydrogen peroxide; β‐hydroxy acyl‐CoA dehydrogenase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Antiretroviral Therapy, Highly Active / trends
  • Cardiolipins / metabolism
  • Citrate (si)-Synthase / metabolism
  • Cross-Sectional Studies
  • Exercise / physiology
  • Exercise Tolerance / physiology
  • HIV Infections / drug therapy
  • HIV Infections / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / physiology

Substances

  • Cardiolipins
  • Citrate (si)-Synthase