Department of Physiology, Comprehensive Alcohol-HIV/AIDS Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
Alcohol Alcohol. 2024 Jul 21;59(5). doi: 10.1093/alcalc/agae060.
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.
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.
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.
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.
由于酒精与 HIV/SIV 感染的相互作用及其对肝脏代谢稳态的影响仍有待充分阐明，本研究旨在确定慢性 binge 饮酒（CBA；每周 13-14g 乙醇/kg，持续 14.5 个月）对接受抗逆转录病毒治疗（ART）的 SIV 喂养的雌性恒河猴的代谢途径的肝适应性的影响。
给恒河猴喂食慢性 binge 酒精（CBA；每周 13-14g 乙醇/kg，持续 14.5 个月；n=7）或载体（VEH；n=8）14.5 个月。在禁食过夜后，取出肝脏。使用冷冻组织测定基因和蛋白质表达、酶活性和脂质含量，并使用石蜡包埋组织进行组织学染色。
与 VEH/SIV 组相比，CBA/SIV 组的肝电子传递复合物 III 的蛋白表达增加，糖酵解（磷酸果糖激酶和醛缩酶）和糖异生（丙酮酸羧化酶）以及与脂质周转稳态相关的基因（脂联素 1、过氧化物酶体增殖物激活受体 γ、碳水化合物反应结合蛋白和乙酰辅酶 A 羧化酶 B）的基因表达增加。血浆甘油三酯浓度与 CBA/SIV 组肝脏甘油三酯含量呈显著正相关。
这些结果反映了 CBA 与葡萄糖和脂质代谢稳态相关的蛋白和基因表达的改变，但没有明显的脂肪肝或糖代谢异常的证据。这些变化是否会使患者在食用更符合 PWH 饮食摄入和/或暴露于其他环境因素的高脂肪/高糖饮食时更容易发生肝脏病理改变，还需要进一步研究。
