Myoblast mitochondrial respiration is decreased in chronic binge alcohol administered simian immunodeficiency virus-infected antiretroviral-treated rhesus macaques

Work from our group demonstrated that chronic binge alcohol (CBA)-induces mitochondrial gene dysregulation at end-stage disease of simian immunodeficiency virus (SIV) infection in antiretroviral therapy (ART) naive rhesus macaques. Alterations in gene expression can disrupt mitochondrial homeostasis and in turn contribute to the risk of metabolic comorbidities characterized by loss of skeletal muscle (SKM) functional mass that are associated with CBA, human immunodeficiency virus (HIV) infection, and prolonged ART. The aim of this study was to examine the interaction of CBA and ART on SKM fiber oxidative capacity and myoblast mitochondrial respiration in asymptomatic SIV-infected macaques. SKM biopsies were obtained and myoblasts isolated at baseline and 11months post-SIV infection from CBA/SIV/ART+ and from sucrose (SUC)-treated SIV-infected (SUC/SIV/ART+) macaques. CBA and ART decreased succinate dehydrogenase (SDH) activity in type 1 and type 2b fibers as determined by immunohistochemistry. Myoblasts isolated from CBA/SIV/ART+ macaques showed decreased maximal oxygen consumption rate (OCR) compared to myoblasts from control macaques. Maximal OCR was significantly increased in control myoblasts following incubation with formoterol, a beta adrenergic agonist, and this was associated with increased PGC-1 expression and mtDNA quantity. Additionally, formoterol treatment of myoblasts isolated from CBA/SIV/ART+ macaques partially restored maximal OCR to levels not significantly different from control. These results show that CBA in combination with ART impairs myoblast mitochondrial homeostasis in SIV-infected macaques. Moreover, our findings suggest that adrenergic agonists can potentially ameliorate mitochondrial dysfunction. Future studies will elucidate whether physical exercise in HIV patients with alcohol use disorder can improve mitochondrial health.