Fostering best practice methods and translation in animal research

Abstract

Maternal nutrition has emerged as an important factor for the long-term health of offspring and has been suggested as a potential contributor to the rapid increase in obesity rates. Growing evidence from animal models suggest prenatal exposure to highly sweetened diets, such as those that contain excess sugar or non-nutritive sweeteners (NNS), may impact offspring metabolism. Animal experiments play a crucial role to help understand mechanistic links between genetic and environmental influences during early life.

The starting point for this body of work synthesised the totality of published scientific evidence through two preclinical systematic reviews investigating maternal NNS and sucrose consumption. Findings highlighted many animal experiments were poorly designed and reported, and often lacked real consideration for animal to human translation.

As a result, we attempted to conduct an animal study to enhanced translation by developing an ecologically valid model of sweetener consumption. Results confirmed rats will consume some commercially available NNS beverages.

However, despite best efforts, uncertainty emerged about the impact my own animal study might have on human health. Reflecting deeply, I could not justify using more animals and decided my research path would be more impactful by advocating for improvement to the scientific quality of animal studies.

As such, this thesis uses a mixed methodological approach to investigate research aims which are broadly separated into two parts, but intrinsically linked by the overarching theme of fostering animal best practice methods and translation. The first part investigates the metabolic effects of a highly sweetened maternal diet and enhancing translational capacity for NNS consumption. And the second part explores the factors that influence early career researchers that use animals, on how they make important decisions during preclinical research and identifies effective strategies to support the researchers.