Effective antiretroviral therapy (ART) has significantly reduced mortality of people living with HIV (PLWH), and the prevalence of at-risk alcohol use is higher among PLWH. Increased survival and aging of PLWH is associated with increased prevalence of metabolic comorbidities especially among menopausal women, and adipose tissue metabolic dysregulation may be a significant contributing factor. We examined the differential effects of chronic binge alcohol (CBA) administration and ovariectomy (OVX) on the omental adipose tissue (OmAT) proteome in a subset of simian immunodeficiency virus (SIV)-infected macaques of a longitudinal parent study. Quantitative discovery-based proteomics identified 1429 differentially expressed proteins. Ingenuity Pathway Analysis (IPA) was used to calculate z-scores, or activation predictions, for functional pathways and diseases. Results revealed protein changes associated with functional pathways centered around the "OmAT metaboproteome profile". Based on z-scores, CBA did not affect functional pathways of metabolic disease but dysregulated proteins involved in AMPK signaling and lipid metabolism. OVX-mediated proteome changes were predicted to promote pathways involved in glucose- and lipid-associated metabolic disease. Proteins involved in apoptosis, necrosis, and reactive oxygen species (ROS) pathways were also predicted to be activated by OVX, and these were predicted to be inhibited by CBA. These results provide evidence for the role of ovarian hormone loss in mediating OmAT metaboproteome dysregulation in SIV and suggest that CBA modifies OVX-associated changes. In the context of OVX, CBA administration produced larger metabolic and cellular effects, which we speculate may reflect a protective role of estrogen against CBA-mediated adipose tissue injury in female SIV-infected macaques.

中文翻译：

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慢性酗酒和卵巢切除术使猴免疫缺陷病毒感染的雌性猕猴的网膜脂肪组织代谢蛋白质组失调

有效的抗逆转录病毒疗法 (ART) 显着降低了 HIV 感染者 (PLWH) 的死亡率，并且在 PLWH 中高风险饮酒的流行率更高。PLWH 的存活率和老龄化增加与代谢合并症的患病率增加有关，尤其是在绝经期妇女中，脂肪组织代谢失调可能是一个重要因素。我们在一项纵向亲本研究的猴免疫缺陷病毒 (SIV) 感染的猕猴子集中检查了慢性狂饮酒精 (CBA) 给药和卵巢切除术 (OVX) 对网膜脂肪组织 (OmAT) 蛋白质组的不同影响。基于定量发现的蛋白质组学鉴定了 1429 种差异表达的蛋白质。Ingenuity Pathway Analysis (IPA) 用于计算 z 分数或激活预测，用于功能通路和疾病。结果揭示了与以“OmAT 代谢蛋白质组谱”为中心的功能通路相关的蛋白质变化。基于 z 分数，CBA 不影响代谢疾病的功能通路，但参与 AMPK 信号传导和脂质代谢的蛋白质失调。据预测，OVX 介导的蛋白质组变化会促进参与葡萄糖和脂质相关代谢疾病的途径。还预测参与细胞凋亡、坏死和活性氧 (ROS) 途径的蛋白质会被 OVX 激活，并且预测这些会被 CBA 抑制。这些结果为卵巢激素损失在介导 SIV 中 OmAT 代谢蛋白质组失调中的作用提供了证据，并表明 CBA 改变了 OVX 相关的变化。在 OVX 的背景下，