Lu Zhaoxu, Qian Ping, Chang Jiahui, He Xuejia, Zhang Haifeng, Wu Jian, Zhang Ting, Wu Jianxin
Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
Front Cell Dev Biol. 2023 Jun 20;11:1199902. doi: 10.3389/fcell.2023.1199902. eCollection 2023.
The effect of exercise on human metabolism is obvious. However, the effect of chronic exercise on liver metabolism in mice is less well described. The healthy adult mice running for 6 weeks as exercise model and sedentary mice as control were used to perform transcriptomic, proteomic, acetyl-proteomics, and metabolomics analysis. In addition, correlation analysis between transcriptome and proteome, and proteome and metabolome was conducted as well. In total, 88 mRNAs and 25 proteins were differentially regulated by chronic exercise. In particular, two proteins (Cyp4a10 and Cyp4a14) showed consistent trends (upregulated) at transcription and protein levels. KEGG enrichment analysis indicated that Cyp4a10 and Cyp4a14 are mainly involved in fatty acid degradation, retinol metabolism, arachidonic acid metabolism and PPAR signaling pathway. For acetyl-proteomics analysis, 185 differentially acetylated proteins and 207 differentially acetylated sites were identified. Then, 693 metabolites in positive mode and 537 metabolites in negative mode were identified, which were involved in metabolic pathways such as fatty acid metabolism, citrate cycle and glycolysis/gluconeogenesis. Based on the results of transcriptomic, proteomics, acetyl-proteomics and metabolomics analysis, chronic moderate intensity exercise has certain effects on liver metabolism and protein synthesis in mice. Chronic moderate intensity exercise may participate in liver energy metabolism by influencing the expression of Cyp4a14, Cyp4a10, arachidonic acid and acetyl coenzyme A and regulating fatty acid degradation, arachidonic acid metabolism, fatty acyl metabolism and subsequent acetylation.
运动对人体新陈代谢的影响是显而易见的。然而，长期运动对小鼠肝脏代谢的影响却鲜有描述。本研究以健康成年小鼠为运动模型，进行6周的跑步运动，并以久坐不动的小鼠作为对照，开展了转录组学、蛋白质组学、乙酰化蛋白质组学和代谢组学分析。此外，还进行了转录组与蛋白质组、蛋白质组与代谢组之间的相关性分析。总计有88种mRNA和25种蛋白质受到长期运动的差异调节。特别值得一提的是，两种蛋白质（Cyp4a10和Cyp4a14）在转录水平和蛋白质水平均呈现一致的上调趋势。KEGG富集分析表明，Cyp4a10和Cyp4a14主要参与脂肪酸降解、视黄醇代谢、花生四烯酸代谢以及PPAR信号通路。在乙酰化蛋白质组学分析中，共鉴定出185种差异乙酰化蛋白和207个差异乙酰化位点。随后，在正模式下鉴定出693种代谢物，在负模式下鉴定出537种代谢物，它们参与了脂肪酸代谢、柠檬酸循环和糖酵解/糖异生等代谢途径。基于转录组学、蛋白质组学、乙酰化蛋白质组学和代谢组学分析结果，长期中等强度运动对小鼠肝脏代谢和蛋白质合成具有一定影响。长期中等强度运动可能通过影响Cyp4a14、Cyp4a10、花生四烯酸和乙酰辅酶A的表达，调节脂肪酸降解、花生四烯酸代谢、脂肪酰代谢及后续乙酰化作用，从而参与肝脏能量代谢。
