Serum metabolomics reveals one-carbon metabolism differences between lean and obese cats not affected by L-carnitine or choline supplementation

Abstract The supplementation of choline and L-carnitine in obese cats has garnered attention as a potential method for preventing and treating feline hepatic lipidosis (FHL). Providing dietary choline above the current recommended allowance to overweight and obese cats may have positive effects on one-carbon metabolism and hepatic lipid mobilization. Research on the metabolomic effects of L-carnitine supplementation in cats, however, remains limited. This study aimed to investigate the individual effects of choline and L-carnitine supplementation on the fasted serum metabolomic profiles of obese (n=9; body condition score [BCS]: 8-9/9) and lean (n=9; BCS: 4-5/9) adult male neutered cats fed at maintenance energy requirements. Cats were fed a commercial extruded cat food top-dressed with choline (6 x National Research Council recommended allowance: 378 mg/kg BW0.67), L-carnitine (200 mg/kg BW), or control (no supplement) in a 3 x 3 complete Latin square design for 6 weeks per treatment, with a 2-week washout between each treatment period. The cats were fed once daily, and BW and BCS were assessed weekly. Fasted serum metabolites were analyzed at the end of each treatment period using direct infusion mass spectrometry (DI-MS) and liquid chromatography-mass spectrometry (LC-MS). The data were analyzed using SAS with proc GLIMMIX, considering group and period as random effects, and treatment, body condition, and their interaction as fixed effects. Statistical significance was set at p < 0.05, and Tukey's post-hoc test was used for multiple comparisons when significance was observed. Obese cats had greater concentrations of s-adenosylhomocysteine, cysteine, cystine, reduced glutathione, and oxidized glutathione (GSSG), suggestive of alterations in one-carbon metabolism with obesity. The oxidation of FA may have improved with both L-carnitine and choline supplementation. While choline and L-carnitine independently affected concentrations of betaine, and GSSG and decarboxylated S-adenosylmethionine, respectively, neither supplement broadly altered one-carbon metabolism. The present study suggests that dysfunction in one-carbon metabolism should be taken into consideration when examining the pathogenesis and increased FHL risk in obese cats.