Li Chenlei, Wang Feifei, Mao Yongxia, Ma Yanfen, Guo Yansheng
College of Animal Science and Technology, Ningxia University, Yinchuan, 750021, China.
Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan, 750021, China.
BMC Genomics. 2025 Jan 6;26(1):10. doi: 10.1186/s12864-024-11067-7.
Trimethylamine N-oxide (TMAO) is a metabolite produced by gut microbiota, and its potential impact on lipid metabolism in mammals has garnered widespread attention in the scientific community. Bovine fatty liver disease, a metabolic disorder that severely affects the health and productivity of dairy cows, poses a significant economic burden on the global dairy industry. However, the specific role and pathogenesis of TMAO in bovine fatty liver disease remain unclear, limiting our understanding and treatment of the condition. This study aims to construct a bovine fatty liver cell model using an integrated approach that combines transcriptomic, proteomic, and metabolomic data. The objective is to investigate the impact of TMAO on lipid metabolism at the molecular level and explore its potential regulatory mechanisms.
We established an in vitro bovine fatty liver cell model and conducted a comprehensive analysis of cells treated with TMAO using high-throughput omics sequencing technologies. Bioinformatics methods were employed to delve into the regulatory effects on lipid metabolism, and several key genes were validated through RT-qPCR. Treatment with TMAO significantly affected 4790 genes, 397 proteins, and 137 metabolites. KEGG enrichment analysis revealed that the significantly altered molecules were primarily involved in pathways related to the pathology of fatty liver disease, such as metabolic pathways, insulin resistance, hepatitis B, and the AMPK signaling pathway. Moreover, through joint analysis, we further uncovered that the interaction between TMAO-mediated AMPK signaling and oxidative phosphorylation pathways might be a key mechanism promoting lipid accumulation in the liver.
Our study provides new insights into the role of TMAO in the pathogenesis of bovine fatty liver disease and offers a scientific basis for developing more effective treatment strategies.
氧化三甲胺（TMAO）是肠道微生物群产生的一种代谢产物，其对哺乳动物脂质代谢的潜在影响已在科学界引起广泛关注。牛脂肪肝疾病是一种严重影响奶牛健康和生产力的代谢紊乱疾病，给全球乳制品行业带来了巨大的经济负担。然而，TMAO在牛脂肪肝疾病中的具体作用和发病机制仍不清楚，这限制了我们对该疾病的理解和治疗。本研究旨在采用整合转录组学、蛋白质组学和代谢组学数据的综合方法构建牛脂肪肝细胞模型。目的是在分子水平上研究TMAO对脂质代谢的影响，并探索其潜在的调控机制。
我们建立了体外牛脂肪肝细胞模型，并使用高通量组学测序技术对用TMAO处理的细胞进行了全面分析。采用生物信息学方法深入研究对脂质代谢的调控作用，并通过RT-qPCR验证了几个关键基因。TMAO处理显著影响了4790个基因、397种蛋白质和137种代谢物。KEGG富集分析表明，显著改变的分子主要参与与脂肪肝疾病病理相关的途径，如代谢途径、胰岛素抵抗、乙型肝炎和AMPK信号通路。此外，通过联合分析，我们进一步发现TMAO介导的AMPK信号与氧化磷酸化途径之间的相互作用可能是促进肝脏脂质积累的关键机制。
我们的研究为TMAO在牛脂肪肝疾病发病机制中的作用提供了新的见解，并为制定更有效的治疗策略提供了科学依据。
