Metabolomic serum abnormalities in dogs with hepatopathies: Congenital portosystemic shunts versus high liver enzyme activities

Background Hepatopathies can cause major metabolic abnormalities due to the liver’s central role in the metabolism.

Objective To determine differences in serum metabolite parameters and metabolomic patterns of dogs with congenital portosystemic shunts (cPSS) and dogs with high serum liver enzyme activities (HLEA).

Methods Left-over serum samples from dogs with cPSS (n=24) and dogs with HLEA (n=25) submitted to a veterinary diagnostic laboratory were analyzed by a validated targeted proton nuclear magnetic resonance (¹H NMR) spectroscopy platform (Bruker 500 MHz) quantifying 123 parameters. Samples from young (≤3 years) and older adult dogs (>3 years) with normal biochemistry and hematological results served as age-related controls (n=32 for both). Uni- and multivariate statistical analyses including partial least squares-discriminant, principal component analyses (PCA) and machine learning approaches were used to compare metabolic parameters and patterns among groups.

Results Both control groups showed very similar metabolomic patterns and were thus combined for further analyses. PCA of the serum metabolome demonstrated distinct clustering of individuals in each group. Nearly all serum metabolite concentrations showed abnormalities including higher concentrations of aromatic amino acids, lower concentrations of branched-chained amino acids (BCAA), and altered fatty acid in cPSS. In contrast, the HLEA group showed increased concentrations of BCAA, phenylalanine, and various lipoproteins. Machine learning models demonstrate excellent classification based on metabolomic data only.

Conclusion Serum metabolomic patterns of dogs with cPSS and HLEA differ significantly from each other and controls. The observed changes may be helpful studying pathophysiology, diagnostic approach, and prognosis.

Publication History

Article published online:
08 March 2022