Myoblast mitochondrial respiration is decreased in chronicbinge alcohol administered simian immunodeficiencyvirus-infected antiretroviral-treated rhesus macaques

Date

2018

Authors

Duplanty, Anthony A.
Siggins, Robert W.
Allerton, Timothy
Simon, Liz
Molina, Patricia E.

Journal Title

Journal ISSN

Volume Title

Publisher

Wiley

Abstract

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.

Description

Article originally published in Physiological Reports, 6(5). English. Published online 2018. https://doi.org/10.14814/phy2.13625

Keywords

Chronic alcohol, HIV, Mitochondria, SIV

Citation

This is the publisher’s version of an article that is available at https://doi.org/10.14814/phy2.13625. Recommended citation: Duplanty, A. A., Siggins, R. W., Allerton, T., Simon, L., & Molina, P. E. (2018). Myoblast mitochondrial respiration is decreased in chronic binge alcohol administered simian immunodeficiency virus-infected antiretroviral-treated rhesus macaques. Physiological Reports, 6(5). https://doi.org/10.14814/phy2.13625. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.

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