Myoblast mitochondrial respiration is decreased in chronicbinge alcohol administered simian immunodeficiencyvirus-infected antiretroviral-treated rhesus macaques
Siggins, Robert W.
Molina, Patricia E.
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Work from our group demonstrated that chronic binge alcohol (CBA)-induces mitochondrial gene dysregulation at end-stage disease of simianimmunodeficiency virus (SIV) infection in antiretroviral therapy (ART) na€ıverhesus macaques. Alterations in gene expression can disrupt mitochondrialhomeostasis and in turn contribute to the risk of metabolic comorbiditiescharacterized by loss of skeletal muscle (SKM) functional mass that are associ-ated with CBA, human immunodeficiency virus (HIV) infection, and pro-longed ART. The aim of this study was to examine the interaction of CBAand ART on SKM fiber oxidative capacity and myoblast mitochondrial respi-ration in asymptomatic SIV-infected macaques. SKM biopsies were obtainedand myoblasts isolated at baseline and 11 months post-SIV infection fromCBA/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 maximaloxygen consumption rate (OCR) compared to myoblasts from control maca-ques. Maximal OCR was significantly increased in control myoblasts followingincubation with formoterol, a beta adrenergic agonist, and this was associatedwith increased PGC-1aexpression and mtDNA quantity. Additionally, for-moterol treatment of myoblasts isolated from CBA/SIV/ART+macaques par-tially restored maximal OCR to levels not significantly different from control.These results show that CBA in combination with ART impairs myoblastmitochondrial homeostasis in SIV-infected macaques. Moreover, our findingssuggest that adrenergic agonists can potentially ameliorate mitochondrial dys-function. Future studies will elucidate whether physical exercise in HIVpatients with alcohol use disorder can improve mitochondrial health. **This article was originally published in Physiological Reports: Duplanty, A., Siggins, R., Allerton, T., Simon, L., & Molina, P. (2018). Myoblast mitochondrial respiration is decreased in chronic binge alcohol administered simian immunodeficiency virus‐infected antiretroviral‐treated rhesus macaques. Physiological Reports, 6(5) doi: 10.14814/phy2.13625.