Metabolomic profiling of serum alterations and biomarker discovery in feline hepatic liposis

Feline hepatic lipidosis (FHL) is a common liver dysfunction caused by metabolic disorders. The objective was to evaluate the metabolic alteration in the cats of FHL and to identify biomarkers that can serve as biomarker for FHL. Differential metabolites in the serum of spontaneous FHL cats (FS, n = 12) and healthy cats (CS group, n = 12) were analyzed using GC/MS metabolomics. Differential metabolites with diagnostic significance were identified through receiver operating characteristic (ROC) curves. The expression level of the differential metabolite 2-hydroxybutyric acid (2-HB) was detected in the serum of the FS and CS groups, and biomarker were established. The biomarker efficacy of 2-HB for FHL was verified using serum samples from cats with FHL caused by different etiologies (F, n = 10) and healthy cats (C, n = 50). There were 13 significantly different metabolites between the CS and FS groups (VIP > 1, P < 0.05) with the area under the ROC curve (AUC) greater than 0.70. The AUC for serum 2-HB was 0.90 (95% confidence interval 0.767-1.000, P < 0.001), with an optimal critical value of 564.8 ng/L. By randomly detecting serum 2-HB in groups F and C (the optimal cut-off value is 564.8 ng/L), the detection rate for FHL diagnosis was 100% and the false positive rate was 0%. In cats with FHL, metabolic changes occur in amino acids, nucleotide sugars, glycerophospholipids, phenylalanine, galactose, alpha-linolenic acid, and glycerides. A serum 2-HB level greater than 564.8 ng/L serves as a biomarker for FHL.