The Journal of nutrition · 2026
Serum Metabolomics Reveals Impaired Fatty Acid Oxidation and Elevated One-Carbon Demand in Cats Fed a Low-Protein Diet Compared with a Low-Fat or Low-Carbohydrate Diet.
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Godfrey Hannah, Yang Jingming, He Emily, Kelly Janelle, Kostiuk Darcia, Blades Jennifer Saunders, Shoveller Anna Kate, Verbrugghe Adronie
Аннотация
BACKGROUND: Feline obesity remains a major metabolic health concern, yet the mechanistic effects of controlled macronutrient substitution on feline metabolism are poorly defined. Cats, as obligate carnivores, have high amino acid oxidation and limited carbohydrate metabolic capabilities that may result in metabolic shifts when dietary protein is substituted for dietary fat or for dietary carbohydrate, as nitrogen-free extract (NFE).
OBJECTIVES: The aim of our study was to apply targeted metabolomics to assess fasted metabolic consequences of an isoenergetic macronutrient substitution diet design in lean and obese cats.
METHODS: Sixteen male neutered cats (LEAN, n = 8; OBESE, n = 8) were fed a low-protein [LP; protein = 28%, fat = 40%, and NFE = 32% metabolizable energy (ME)], low-fat (protein = 40%, fat = 30%, and NFE = 30%ME), or low-carbohydrate (protein = 36%, fat = 41%, and NFE = 23%ME) diet, to maintain body weight, in a 3 × 3 Latin square design for 3 periods of 4 wk. Serum from cats who were deprived of food collected on day 24 was analyzed using direct flow injection mass spectrometry (143 metabolites) and nuclear magnetic resonance spectroscopy (23 metabolites). Data were analyzed using mixed models for the effects of body condition and dietary treatment.
RESULTS: LP resulted in greater serum concentrations of homocysteine and betaine (P < 0.05), indicating greater one-carbon demand and elevated short- and long-chain acylcarnitines (P < 0.05) suggesting restricted mitochondrial fatty acid oxidation. Lower serum urea and total dimethylarginine concentrations (P < 0.05) in LP suggested increased reliance on endogenous protein pools for amino acids under protein restriction. LEAN showed greater reductions in long-chain phosphatidylcholine and lysophosphatidylcholine concentrations than OBESE when consuming LP (P < 0.05), indicating greater metabolic flexibility in LEAN. OBESE also displayed elevated branched-chain amino acids and organic acids (P < 0.05), regardless of diet, reflecting metabolic dysregulation, and protein degradation.
CONCLUSIONS: Targeted metabolomics demonstrated that reducing dietary protein and substituting with dietary fat produces metabolic signatures consistent with impaired fatty acid oxidation, greater one-carbon demand, and protein turnover in cats, underscoring the importance of dietary protein-fat balance in feline metabolic health.
OBJECTIVES: The aim of our study was to apply targeted metabolomics to assess fasted metabolic consequences of an isoenergetic macronutrient substitution diet design in lean and obese cats.
METHODS: Sixteen male neutered cats (LEAN, n = 8; OBESE, n = 8) were fed a low-protein [LP; protein = 28%, fat = 40%, and NFE = 32% metabolizable energy (ME)], low-fat (protein = 40%, fat = 30%, and NFE = 30%ME), or low-carbohydrate (protein = 36%, fat = 41%, and NFE = 23%ME) diet, to maintain body weight, in a 3 × 3 Latin square design for 3 periods of 4 wk. Serum from cats who were deprived of food collected on day 24 was analyzed using direct flow injection mass spectrometry (143 metabolites) and nuclear magnetic resonance spectroscopy (23 metabolites). Data were analyzed using mixed models for the effects of body condition and dietary treatment.
RESULTS: LP resulted in greater serum concentrations of homocysteine and betaine (P < 0.05), indicating greater one-carbon demand and elevated short- and long-chain acylcarnitines (P < 0.05) suggesting restricted mitochondrial fatty acid oxidation. Lower serum urea and total dimethylarginine concentrations (P < 0.05) in LP suggested increased reliance on endogenous protein pools for amino acids under protein restriction. LEAN showed greater reductions in long-chain phosphatidylcholine and lysophosphatidylcholine concentrations than OBESE when consuming LP (P < 0.05), indicating greater metabolic flexibility in LEAN. OBESE also displayed elevated branched-chain amino acids and organic acids (P < 0.05), regardless of diet, reflecting metabolic dysregulation, and protein degradation.
CONCLUSIONS: Targeted metabolomics demonstrated that reducing dietary protein and substituting with dietary fat produces metabolic signatures consistent with impaired fatty acid oxidation, greater one-carbon demand, and protein turnover in cats, underscoring the importance of dietary protein-fat balance in feline metabolic health.