Abstract Background Feline hepatic lipidosis (FHL) lacks well-defined metabolic biomarkers and mechanistic understanding. Hypothesis/Objectives Clarify the metabolic biomarkers and mechanisms of FHL. Animals Two groups of cats were analyzed: 14 cats (7 FHL cases and 7 healthy controls) for liver metabolomics, and 60 cats (10 FHL cases and 50 healthy controls) for blood 3-hydroxybutyrate (3-HB) testing. Methods Hepatic lipidosis was confirmed by histopathological assessment and ultrasonography. Untargeted metabolomics was performed using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS), with pathway analysis using MetaboAnalyst 5.0. Serum 3-HB was quantified using an enzymatic assay. Statistical analysis included principal component analysis, orthogonal partial least squares discriminant analysis, cross-validation, permutation tests, and F₁ score evaluation for model validation. Results Gas chromatography–mass spectrometry identified four metabolites with variable importance in projection 1 (bootstrap 95% stability range, 0.9-1.3) and 0.05, whereas LC–MS identified 243 differentially abundant metabolites (101 upregulated, 142 downregulated), with 19 demonstrating diagnostic potential (area under the curve AUC 0.7). Pathway analysis identified perturbations in vitamin B6 metabolism (P = .003) and fructose/mannose metabolism (P .001). Serum 3-HB underwent analytical validation in 60 specimens (10 FHL cases, 50 healthy controls), which identified concordant hepatic and systemic increases in FHL. At the optimal cutoff (2.43 mmol/L), it achieved an AUC of 0.86 (95% confidence interval CI, 0.65-1.00) with 92% sensitivity (95% CI, 89%-100%) and 88% specificity (95% CI, 74%-100%) in distinguishing FHL from normal liver under controlled laboratory conditions. Conclusions and clinical importance Preliminary data suggest FHL involves dysregulated fatty acid and vitamin B6 metabolism. Although serum 3-HB shows promise, future studies should include disease controls (eg, cholangitis, hepatitis) to establish specificity. These findings provide foundational insights for mechanistic research.
Xu et al. (Thu,) studied this question.