Chronic binge alcohol mediated hepatic metabolic adaptations in SIV-infected female rhesus macaques

Abstract

Aims: As the interactions of alcohol and HIV/SIV infection and their impact on liver metabolic homeostasis remain to be fully elucidated, this study aimed to determine alcohol-mediated hepatic adaptations of metabolic pathways in SIV/ART-treated female rhesus macaques fed a nutritionally balanced diet.

Methods: Macaques were administered chronic binge alcohol (CBA; 13-14 g ethanol/kg/week for 14.5 months; n = 7) or vehicle (VEH; n = 8) for 14.5 months. Livers were excised following an overnight fast. Gene and protein expression, enzymatic activity, and lipid content were determined using frozen tissue and histological staining was performed using paraffin-embedded tissue.

Results: CBA/SIV macaques showed increased hepatic protein expression of electron transport Complex III and increased gene expression of glycolytic (phosphofructokinase and aldolase) and gluconeogenic (pyruvate carboxylase) enzymes and of genes involved in lipid turnover homeostasis (perilipin 1, peroxisome proliferator-activated receptor gamma, carbohydrate responsive binding protein, and acetyl-CoA carboxylase B) as compared to that of livers from the VEH/SIV group. Plasma triglyceride concentration had a significant positive association with liver triglyceride content in the CBA/SIV group.

Conclusions: These results reflect CBA-associated alterations in expression of proteins and genes involved in glucose and lipid metabolism homeostasis without significant evidence of steatosis or dysglycemia. Whether these changes predispose to greater liver pathology upon consumption of a high fat/high sugar diet that is more aligned with dietary intake of PWH and/or exposure to additional environmental factors warrants further investigation.

Keywords: chronic binge alcohol; female; hepatic metabolism; liver; macaque.