Alcohol Impairs Bioenergetics and Differentiation Capacity of Myoblasts from Simian Immunodeficiency Virus-Infected Female Macaques

Int J Mol Sci. 2024 Feb 19;25(4):2448. doi: 10.3390/ijms25042448.

Abstract

Alcohol misuse and HIV independently induce myopathy. We previously showed that chronic binge alcohol (CBA) administration, with or without simian immunodeficiency virus (SIV), decreases differentiation capacity of male rhesus macaque myoblasts. We hypothesized that short-term alcohol and CBA/SIV would synergistically decrease differentiation capacity and impair bioenergetic parameters in female macaque myoblasts. Myoblasts from naïve (CBA-/SIV-), vehicle [VEH]/SIV, and CBA/SIV (N = 4-6/group) groups were proliferated (3 days) and differentiated (5 days) with 0 or 50 mM ethanol (short-term). CBA/SIV decreased differentiation and increased non-mitochondrial oxygen consumption rate (OCR) versus naïve and/or VEH/SIV. Short-term alcohol decreased differentiation; increased maximal and non-mitochondrial OCR, mitochondrial reactive oxygen species (ROS) production, and aldolase activity; and decreased glycolytic measures, ATP production, mitochondrial membrane potential (ΔΨm), and pyruvate kinase activity. Mitochondrial ROS production was closely associated with mitochondrial network volume, and differentiation indices were closely associated with key bioenergetic health and function parameters. Results indicate that short-term alcohol and CBA non-synergistically decrease myoblast differentiation capacity. Short-term alcohol impaired myoblast glycolytic function, driving the bioenergetic deficit. Results suggest potentially differing mechanisms underlying decreased differentiation capacity with short-term alcohol and CBA, highlighting the need to elucidate the impact of different alcohol use patterns on myopathy.

Keywords: HIV; alcohol use disorder; antiretroviral therapy; ethanol; glycolysis; mitochondria; myopathy; satellite cell; skeletal muscle.

MeSH terms

  • Animals
  • Binge Drinking*
  • Energy Metabolism
  • Ethanol / pharmacology
  • Female
  • Macaca mulatta
  • Male
  • Muscular Diseases* / complications
  • Myoblasts
  • Reactive Oxygen Species
  • Simian Acquired Immunodeficiency Syndrome* / complications
  • Simian Immunodeficiency Virus*
  • Viral Load

Substances

  • Reactive Oxygen Species
  • Ethanol