Nature, Nurture, Neutering & Nutrition: Metabolomic Insights into the Mysteries of Cat Metabolism
We asked David Allaway, PhD, Senior Research Scientist in Nutrition & Metabolism, to tell us about his recently published study and what he learned by working with Metabolon.
Mars Petcare is one of the world’s leading pet care providers and features 41 well-known brands, including PEDIGREE®, IAMS®, WHISKAS®, ROYAL CANIN® and BANFIELD®. The company’s WALTHAM Centre for Pet Nutrition is using cutting-edge technology in its research to better understand pet metabolism and create healthier foods and supplements. We asked David Allaway, PhD, Senior Research Scientist in Nutrition & Metabolism, to tell us about his recently published study and what he learned by working with Metabolon.
Why did you decide to run this study?
As with humans, excess weight is an increasingly common health issue for both cats and dogs. In cats, neutering is known to be a significant risk factor for obesity. However, the mechanisms that promote this neuter-associated weight gain are not well understood. For instance, there can be an acute increase in body weight in the weeks following neutering. Researchers have speculated whether this is due to an increased drive to eat more food, or reduced energy requirements, or a combination of both. Whilst it has been shown that providing neutered female kittens with estrogen can mitigate weight gain, the issues are less well understood in males. Without a clear hypothesis to test, we chose metabolomics. This allows us to obtain data to develop the “best hypothesis” to test in future studies.
The aim of this study was to find out whether:
i. cats need less food after neutering to maintain their healthy body weight, and
ii. sexual development prior to neutering would lead to a different energy requirements needs.
What did you find out?
The metabolomics analysis indicated that neutering did not cause a detectable shift in energy metabolism that would explain any reduction in dietary intake. We also found that the age at which neutering took place had little impact on the fasted plasma metabolome beyond 12 weeks after the procedure.
This study also provided us with a wealth of information related to age, sexual development and neutering. This is one of the major benefits of using metabolomics in a non-hypothesis-driven study. We were able to analyse many metabolites across a range of metabolic pathways to establish which were most important.
In the paper, we reported a number of interpretations of the data that are fascinating. In particular, we saw the potential physiological costs of using a valuable commodity, such as a S-amino acid derivative, as a signalling device for conspecifics. We also potentially identified a transition in liver function/maturation that occurs around 20 weeks of age.
Why does neutering matter to pet nutrition?
At WALTHAM, we want to understand more about the impact of neutering, a known risk factor for obesity. Of particular interest are any potential changes in the nutritional requirements for neutered kittens. With this information, Mars Petcare can make the appropriate changes to products or feeding guidelines, if required. In addition, knowledge and best practices can be shared with regulatory authorities, vets and owners. Our research is revealing the range of energy requirements needed to support healthy kitten growth and how neutering might impact this.
How is metabolomics useful in aiding a fundamental understanding of pet health and nutrition?
We’ve used metabolomics in various studies, and though the purposes may be very different, the theme is consistent: it generates insights that can guide future hypothesis-led studies. Metabolomics provides a vast range of metabolite data from accessible biofluids. This reflects systemic changes in metabolism that help us understand what metabolic differences exist between groups (such as breed, gender or neuter group). The appropriate interpretation of these data can improve understanding of the influence of diet on metabolism in healthy animals.
Robust, data-led analysis is especially useful for cats as they are obligate carnivores and don’t conform to the classical paradigm of mammalian energy metabolism. Instead, numerous adaptations support increased protein oxidation and manage reduced carbohydrate intake. Metabolomics has already helped us reveal how such adaptations may influence how cats respond to diets differently to dogs. The approach has also identified confounding factors that may affect data interpretation collected in hypothesis-driven nutrition studies. This is incredibly important for our research, which is always conducted in accordance with the 3Rs principle to replace, reduce and refine the number of individuals required in a study. Of course, there are challenges, too. As we undertake more metabolomics studies, we continually improve our study designs to support better interpretation of these data we collect.
How did Metabolon’s technology help?
The various analytical platforms allowed many different, chemically diverse metabolites to be measured. This was important for non-hypothesis driven experimental design. It allowed changes of lipids associated with age to be identified, as well as amino acid derivatives associated with sexual development and neutering. Without a broad panel of metabolites, especially the feline-specific felinine derivatives, we would not have been able to contextualize the data to make the interpretations we made.
What are the implications for your findings?
I would like to think that the study may have provided food for thought to others interested in cat health, metabolism, sexual development and weight management, as well as the physiological costs associated with conspecific signalling. It would be nice to think that future studies from other labs could incorporate evidence from the robust analysis and interpretation that we have provided here.