164 Combining in silico, in vitro, and in vivo approaches for studying taste perception and preferences of domestic cats and dogs

Abstract Developing food products for pet cats and dogs is an important and challenging area of the food industry. The diet offered must be both balanced and palatable to ensure the amount of food eaten meets their nutritional requirements. The taste perception of pets is different from humans in many cases (Li et al., 2005) and therefore species-specific research is necessary. Hence, understanding the flavor preferences of cats and dogs is an important area of research and requires multiple disciplines and scientific approaches. We have developed a range of complimentary methods for studying taste perception and preferences of domestic cats and dogs In silico: homology models of the pet taste receptors have been developed. These models are used to identify candidate compounds and elucidate the mechanisms of taste perception of pets. In vitro: cell-based high throughput screening assays of pet taste receptors have also been developed. These assays are used to identify taste-active compounds and confirm response to those identified via the in silico method to refine the model. In vivo: finally, a two-bottle choice test for cats has been developed. This test is used to confirm hedonic responses and determine optimum concentrations of single compounds and mixtures identified by the in silico and/or in vitro methods. Using this novel approach, we now have a deeper understanding of the taste perception and preferences of pets, with specific examples including Umami (McGrane et al., 2023) and Kokumi (Laffitte et al., 2021) taste perception of cats and bitter taste perception of dogs (Gibbs et al., 2022). This approach has also enabled us to reduce the number of in vivo tests required, so implementing the 3Rs, by prioritizing the most promising tastants using the in silico and in vitro methods. Gibbs, M., Winnig, M., Riva, I., Dunlop, N., Waller, D., Klebansky, B., Logan, D.W., Briddon, S.J., Holliday, N.D., McGrane, S.J. 2022. Bitter taste sensitivity in domestic dogs (Canis familiaris) and its relevance to bitter deterrents of ingestion. PLoS One. 17:e0277607. Laffitte, A., Gibbs, M., Hernangomez de Alvaro, C., Addison, J., Lonsdale, Z.N., Giribaldi, M.G., Rossignoli, A., Vennegeerts, T., Winnig, M., Klebansky, B., Skiles, J., Logan, D.W., McGrane, S.J. 2021. Kokumi taste perception is functional in a model carnivore, the domestic cat (Felis catus). Sci Reports 2021 111. 11:1–17. Li, X., Li, W., Wang, H., Cao, J., Maehashi, K., Huang, L., Bachmanov, A.A., Reed, D.R., Legrand-Defretin, V., Beauchamp, G.K., Brand, J.G. 2005. Pseudogenization of a sweet-receptor gene accounts for cats’ indifference toward sugar. PLoS Genet. 1:0027–0035.McGrane, S.J., Gibbs, M., Hernangomez De Alvaro, C., Dunlop, N., Winnig, M., Klebansky, B., Waller, D. 2023. Umami taste perception and preferences of the domestic cat (Felis catus), an obligate carnivore. Chem Senses. 48.