Vetsuisse Faculty, University of Zürich, 8057, Zürich, Switzerland.
Laboklin GmbH & Co. KG, 97688, Bad Kissingen, Germany.
Sci Rep. 2022 Mar 29;12(1):5329. doi: 10.1038/s41598-022-09056-5.
Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.
肝病变可导致人类和动物发生重大代谢异常。本研究比较了先天性门腔分流(cPSS,n=24)或高血清肝酶活性(HLEA,n=25)犬与对照组犬(n=64)剩余血清样本中血清代谢组学参数和模式的差异。使用经过验证的靶向质子核磁共振波谱平台评估了 123 个参数。血清代谢组的主成分分析表明,每组个体之间存在明显的聚类,与其他组相比,HLEA 组的聚类更宽,可能是由于这些样本中代表的肝脏疾病谱更广。虽然年轻和老年成年对照组犬的代谢组模式和聚类非常相似,但在肝病变组中存在许多代谢物的变化。与对照组相比,cPSS 犬的苯丙氨酸和酪氨酸浓度较高,支链氨基酸(BCAA)浓度较低,脂肪酸参数也发生了改变。相比之下,HLEA 犬的 BCAA、苯丙氨酸和各种脂蛋白浓度升高。仅基于代谢组学数据的机器学习显示出出色的分组分类能力,可能为鉴别肝病变提供了一种新的工具。观察到的代谢参数变化可能为肝病变的病理生理学、诊断和预后提供宝贵的见解。