Profound Perturbation in the Metabolome of a Canine Obesity and Metabolic Disorder Model

Abstract

Canine models are increasingly being used in metabolic studies due to their physiological similarity with humans. The present study aimed to identify changes in metabolic pathways and biomarkers with potential clinical utility in a canine model of obesity and metabolic disorders induced by a high-fat diet (HFD). Eighteen male beagles were included in this study, 9 of which were fed a HFD for 24 weeks, and the remaining 9 were fed normal chow (NC) during the same period. Plasma and urine samples were collected at weeks 12 and 24 for untargeted metabolomic analysis. Dogs fed a HFD showed a gradual body weight increase during the feeding period and had hyperlipidemia, increased leukocyte counts, and impaired insulin sensitivity at week 24. Plasma and urine metabonomics analysis displayed clear separations between the HFD-fed and NC-fed dogs. A total of 263 plasma metabolites varied between the two groups, including stearidonic acid, linolenic acid, carnitine, long-chain ceramide, 3-methylxanthine, and theophylline, which are mainly engaged in fatty acid metabolism, sphingolipid metabolism, and caffeine metabolism. A total of 132 urine metabolites related to HFD-induced obesity and metabolic disorders were identified, including 3-methylxanthine, theophylline, pyridoxal 5’-phosphate, and harmine, which participate in pathways such as caffeine metabolism and vitamin digestion and absorption. Eight metabolites with increased abundance (e.g., 3-methylxanthine, theophylline, and harmine) and 4 metabolites with decreased abundance (e.g., trigonelline) in both the plasma and urine of the HFD-fed dogs were identified. In conclusion, the metabolomic analysis revealed molecular events underlying a canine HFD model and identified several metabolites as potential targets for the prevention and treatment of obesity-related metabolic disorders.