感染 SIV 的雌性猕猴的肝脏代谢适应性由慢性暴饮暴食酒精介导。

IF 2.1 4区 医学 Q3 SUBSTANCE ABUSE
Eden M Gallegos, Liz Simon, Patricia E Molina
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引用次数: 0

摘要

目的:由于酒精与 HIV/SIV 感染之间的相互作用及其对肝脏代谢平衡的影响仍有待全面阐明,本研究旨在确定酒精介导的肝脏代谢通路对喂食营养均衡饮食的 SIV/ART 治疗雌性猕猴的适应性:给猕猴注射慢性暴饮暴食酒精(CBA;13-14 克乙醇/千克/周,持续 14.5 个月;n = 7)或车辆(VEH;n = 8),持续 14.5 个月。隔夜禁食后切除肝脏。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:结果:CBA/SIV猕猴的肝脏电子传递复合体III蛋白表达量增加,糖酵解酶(磷酸果糖激酶和醛缩酶)和葡萄糖酵解酶(丙酮酸羧化酶)的基因表达量增加,参与脂质代谢平衡的基因(过脂素1、过氧化物酶体增殖激活受体γ、碳水化合物反应结合蛋白和乙酰-CoA 羧化酶 B)。在CBA/SIV组中,血浆甘油三酯浓度与肝脏甘油三酯含量呈显著正相关:结论:这些结果反映了与 CBA 相关的参与葡萄糖和脂质代谢平衡的蛋白质和基因表达的改变,但没有明显的脂肪变性或血糖异常的证据。这些变化是否会导致肝脏在摄入高脂/高糖饮食后发生更大的病变,这与 PWH 的膳食摄入量和/或暴露于其他环境因素的情况更加一致,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chronic binge alcohol mediated hepatic metabolic adaptations in SIV-infected female rhesus macaques.

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.

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来源期刊
Alcohol and alcoholism
Alcohol and alcoholism 医学-药物滥用
CiteScore
4.70
自引率
3.60%
发文量
62
审稿时长
4-8 weeks
期刊介绍: About the Journal Alcohol and Alcoholism publishes papers on the biomedical, psychological, and sociological aspects of alcoholism and alcohol research, provided that they make a new and significant contribution to knowledge in the field. Papers include new results obtained experimentally, descriptions of new experimental (including clinical) methods of importance to the field of alcohol research and treatment, or new interpretations of existing results. Theoretical contributions are considered equally with papers dealing with experimental work provided that such theoretical contributions are not of a largely speculative or philosophical nature.
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