Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows. We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings. This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.

中文翻译：

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线粒体中的蛋白质乙酰化在脂肪肝疾病的发病机理中起关键作用。

脂肪肝是负能量平衡导致奶牛围产期疾病的高发，严重威胁产后健康和产奶量。据报道，赖氨酸乙酰化在物质和能量代谢中起重要作用。可以预见，肝脏中作为重要的代谢器官的大多数代谢过程都会发生乙酰化。比较性的乙酰酶组研究被用于量化重度脂肪肝组和正常组的肝组织。结合生物信息学分析，本研究为乙酰化修饰在奶牛脂肪肝疾病中的作用提供了新见解。我们在665种蛋白质上鉴定了1841个差异乙酰化位点。其中，对393个蛋白质上的1072个位点进行了定量。功能富集分析表明，较高乙酰化的蛋白质在能量代谢途径中显着富集，而较低乙酰化的蛋白质在与免疫应答相关的途径（如药物代谢和癌症）中显着富集。在显着乙酰化的蛋白质中，许多线粒体蛋白质被鉴定为与多种蛋白质相互作用并参与脂质代谢。此外，这项研究还确定了潜在的重要蛋白质，例如HADHA，ACAT1和EHHADH，它们可能是奶牛脂肪肝疾病发展过程中乙酰化修饰和人类NAFLD可能治疗靶标的重要调控因子。这项研究提供了奶牛脂肪肝的全面的乙酰酶谱，并揭示了与蛋白质乙酰化相关的重要生物学途径发生在线粒体中，这些途径参与了脂肪肝疾病发病机理的调控。此外，潜在的重要蛋白质，例如HADHA，ACAT1，EHHADH，被预测为脂肪肝疾病发病机理中的重要调节剂。这项工作将有助于了解NAFLD的发病机理，并启发开发NAFLD的新治疗策略。