Chronic Binge Alcohol (CBA) Decreases Skeletal Muscle Oxidative Capacity in Simian Immunodeficiency Virus (SIV)‐Infected Macaques

Abstract

Chronic HIV infection is associated with insulin resistance and increased lipodystrophy. Skeletal muscle (SKM) represents a major site for glucose and lipid oxidation. Acute and chronic alcohol exposure inhibits skeletal muscle glucose metabolism and potentially promotes insulin resistance. We sought to determine the effects of daily CBA or isocaloric sucrose (SUC) administration to male SIV-infected rhesus macaques on SKM muscle fiber type and oxidative capacity. SKM samples (quadriceps) were collected at necropsy after 11 months of SIV infection from CBA/SIV (n=5) or SUC/SIV (n=3) macaques. Serial cross sections (10 μm) were stained for myosin ATPase to determine fiber type population and succinate dehydrogenase (SDH) to measure oxidative capacity. Both SUC/SIV and CBA/SIV animals had decreased (33.2 and 28.2%) number of type 1 (oxidative) fibers and a larger proportion of type 2b (glycolytic) fibers compared to naïve uninfected animals (42%) (n=2). SDH activity, measured by optical density, was significantly lower in the type 1 fibers of both SUC/SIV (OD=87.8) and CBA/SIV (OD=90.7) when compared to controls (OD=120.7). Analysis of SDH activity across all muscle fibers demonstrated a significant reduction in total oxidative capacity in CBA/SIV (OD=146.6) compared to naïve (OD=268.3) and SUC/SIV (OD=195.4) groups. These results demonstrate a reduction in the oxidative capacity of SKM fibers in SIV-infected animals that is further exacerbated by CBA. This research was supported by grants AA07577, AA09803 and AA11290 from the NIAAA/NIH