Senior Principal Scientist Hill's Pet Nutrition Topeka, KS, United States
Abstract:
Background: Immunometabolic responses of cats and dogs to lipopolysaccharide (metabolic endotoxemia; MetTox) is unknown, despite MetTox being associated with disease. To assess responses of cats and dogs without exposure to lipopolysaccharide, cultured whole blood was subjected to lipopolysaccharide challenge ex vivo and analyzed by untargeted metabolomics.
Objective: Assess ex vivo whole blood immunometabolic response of both species to lipopolysaccharide.
Animals: Adult dogs (6) and cats (6) housed at Hill’s Pet Nutrition Center.
Methods: Blood drawn according to animal welfare protocols, incubated +/- lipopolysaccharide. After 24 or 48 hours, supernatants were collected for metabolomic analysis. Metabolites analyzed using a split-plot ANOVA with hour (whole-plot), lipopolysaccharide treatment and interaction (subplot).
Results: Metabolites classified into pathway analysis. Fatty acids decreased in response to lipopolysaccharide in cats but not dogs. In response to lipopolysaccharide both species declined in glucose and increased in lactate while pyruvate increased only in dog. With lipopolysaccharide, both species increased in tryptophan metabolites including kynurenine (dogs) and kynurenate (cats). Also, with lipopolysaccharide dogs had decreased betaine and S-adenosylhomocysteine while cats had only increased S-adenosylhomocysteine . Both species had decreased pyridoxine in the presence of lipopolysaccharide, while only cats had increased levels of the immune modulator itaconate.
Conclusions: The cat is more reliant on fatty acids in a heightened immune response using ex vivo challenge and may benefit from decreased dietary carbohydrate and increased fat as compared to the dog. Both dogs and cats have demands on single carbon metabolism and may benefit from increased dietary betaine for optimal immune response.
