Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA231

Poster Communications

Skeletal muscle and adipose mechanisms contributing to metabolic dysfunction in chronic alcohol administered simian immunodeficiency virus-infected male macaques

L. Simon1,2, P. Molina1,2

1. Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States. 2. Comprehensive Alcohol/HIV-AIDS Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States.


Alcohol use disorders (AUD) occur frequently in people living with HIV/AIDS (PLWHA). The risk of comorbid conditions such as myopathy, insulin resistance, and lipodystrophy arising from both chronic alcohol consumption and HIV infection has risen significantly with the increased survival due to antiretroviral therapy (ART). Our studies have identified loss of skeletal muscle mass as a critical determinant of time to end-stage disease in chronic binge alcohol (CBA) administered non-ART simian immunodeficiency virus (SIV)-infected (CBA/SIV) male rhesus macaques. Moreover, we have shown decreased whole body insulin sensitivity in asymptomatic CBA/SIV macaques irrespective of ART status. We examined the underlying skeletal muscle and adipose tissue alterations in functional phenotype that could contribute to progression of metabolic dysfunction in CBA/SIV macaques. Skeletal muscle isolated at 11 months post-SIV showed decreased anabolic signaling, enhanced pro-inflammatory cytokine expression and collagen deposition, increased expression of ubiquitin ligases and myostatin expression that was associated with and decreased myogenic potential of muscle stem cells in CBA/SIV vs. sucrose (SUC/SIV) macaques. Mesenteric adipose tissue showed decreased adipocyte size, increased inflammatory cell infiltration, and increased collagen deposition, which we predict leads to decreased differentiation of adipose derived-stem cells isolated from CBA/SIV macaques. These findings suggest that CBA exacerbates dysregulation of skeletal muscle and adipose tissue phenotype contributing to metabolic dysfunction in SIV infection. Future studies are aimed to determine the metabolic interrelationship and cross-talk of signals between skeletal muscle and adipose tissue contributing to metabolic dysregulation in SIV infection.

Where applicable, experiments conform with Society ethical requirements