Ringseis Robert, Grundmann Sarah M, Schuchardt Sven, Most Erika, Eder Klaus
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany.
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Nikolai-Fuchs-Str.1, 30625 Hannover, Germany.
Metabolites. 2021 Aug 25;11(9):573. doi: 10.3390/metabo11090573.
Administration of pivalate has been demonstrated to be suitable for the induction of secondary carnitine deficiency (CD) in pigs, as model objects for humans. In order to comprehensively characterize the metabolic effects of secondary CD in the liver of pigs, the present study aimed to carry out comparative analysis of the hepatic transcriptome and hepatic and plasma metabolome of a total of 12 male 5-week-old pigs administered either pivalate (group PIV, = 6) or vehicle (group CON, = 6) for 28 days. Pigs of group PIV had approximately 40-60% lower concentrations of free carnitine and acetylcarnitine in plasma, liver and different skeletal muscles than pigs of group CON ( < 0.05). Transcript profiling of the liver revealed 140 differentially expressed genes (DEGs) between group PIV and group CON (fold change > 1.2 or <-1.2, -value < 0.05). Biological process terms dealing with the innate immune response were found to be enriched with the DEGs ( < 0.05). Using a targeted metabolomics approach for the simultaneous quantification of 630 metabolites, 9 liver metabolites and 18 plasma metabolites were identified to be different between group PIV and group CON ( < 0.05). Considering the limited alterations of the hepatic transcriptome and of the liver and plasma metabolome, it can be concluded that pivalate-induced secondary CD is not associated with significant hepatic metabolism changes in pigs.
已证明给予特戊酸盐适合诱导猪出现继发性肉碱缺乏症（CD），猪可作为人类的模型对象。为全面表征猪肝脏中继发性CD的代谢效应，本研究旨在对总共12头5周龄雄性猪的肝脏转录组以及肝脏和血浆代谢组进行比较分析，这些猪分别给予特戊酸盐（PIV组，n = 6）或赋形剂（CON组，n = 6），持续28天。与CON组猪相比，PIV组猪的血浆、肝脏和不同骨骼肌中的游离肉碱和乙酰肉碱浓度低约40 - 60%（P < 0.05）。肝脏转录谱分析显示PIV组和CON组之间有140个差异表达基因（DEG）（倍数变化> 1.2或< -1.2，P值< 0.05）。发现与先天免疫反应相关的生物学过程术语在DEG中富集（P < 0.05）。采用靶向代谢组学方法同时定量630种代谢物，确定PIV组和CON组之间有9种肝脏代谢物和18种血浆代谢物存在差异（P < 0.05）。考虑到肝脏转录组以及肝脏和血浆代谢组的变化有限，可以得出结论，特戊酸盐诱导的继发性CD与猪肝脏代谢的显著变化无关。
