190 The Nutrigenomic Effects of Dietary Choline and L-Carnitine on the Muscle and Liver of Lean and Overweight Cats

Abstract

Abstract The objective of this study was to investigate the effects of dietary choline and L-carnitine on the lipotropic gene expression in the muscle and liver of overweight and lean cats, when fed for body weight (BW)maintenance. Overweight [n = 6, body fat percent (BF%): 33.2 ± 1.38] and lean (n = 6, BF%:18.4 ± 0.93), 1-2 year old, male, neutered cats received choline (378 mg/kg BW0.67), L-carnitine (200 mg/kg BW) and no supplementation (control) in a 3x3 Latin square design for 6 weeks, with a 2-week washout between treatments periods. Each treatment was offered with a commercial extruded diet; diet amount was provided to maintain current BW. Cats were anesthetized and quadriceps vastus lateralis (30-50 mg) and liver (30-50 mg) biopsies were harvested after each treatment period using an open muscle or laparoscopic biopsy technique respectively. Tissue RNA was isolated with TRIzol and sequenced using directional PolyA RNA-seq. The expressed genes were aligned using the reference genome, Felis_catus_9.0, Ensembl v.107. Differential gene expression was analyzed for 29,928 genes with SEQUIN, using edgeR and TMM normalization. Pathway analysis was performed using EnrichR databases, BioPlanet 2019 and KEGG 2021. Using a two-group comparison, global analysis revealed 92 and 759 differentially expressed genes in the liver and muscle, respectively of overweight cats compared with lean (P < 0.05). Affected pathways included fat digestion and absorption, including peroxisome proliferator-activated receptor (PPAR) signaling in the liver, and immunity related pathways in muscle (P < 0.05). Upon further analysis using a two-group comparison between overweight and lean cats for each treatment, 11 and 692 significant genes were found in choline treated liver samples and L-carnitine treated muscle samples, respectively (P < 0.05). Similar to the global analysis, genes related to fat metabolism, including PPAR signaling, were significant in the choline treated liver samples, and immunity related genes were significant in the L-carnitine treated muscle samples (P < 0.05). Based on preliminary data, supplemental dietary choline may be beneficial for overweight cats as it may increase fat metabolism in the liver, mitigating risks associated with feline hepatic lipidosis (FHL). Supplemental dietary L-carnitine may also be beneficial due to its effects on immunity related pathways, including pathogen defense. To investigate the full effects of choline and L-carnitine on gene expression, further studies are warranted including older, chronically obese cats, as well as confirmed cases of FHL. Acknowledgements: Natural Sciences and Engineering Council of Canada, Elmira Pet Products and Balchem Corp.