Longitudinal Imaging of Maternal Exercise and Exerkine Effects on Offspring Metabolism

Project Summary/Abstract Exercise is increasingly being seen as an effective form of therapy against many diseases. Maternal exercise, especially during pregnancy, has long-lasting effects on childhood wellbeing. Part of these beneficial effects come from the secretion of exercise-induced hormones called exerkines. While research into exercise and exerkines as medicines continue to grow, methods to longitudinally quantify exercise efficacy remain to be elucidated. This research builds tools and methods to track exercise efficacy using metabolic imaging. We hypothesize that exercise in mice will result in activation of brown adipose tissue (BAT). This metabolic activation can be detected using hyperpolarized magnetic resonance imaging (HP-MRI). HP-MRI is a cutting- edge metabolic imaging platform that can quantify metabolic flux. HP is a method that increases the sensitivity of non-radioactive, stable carbon-13 labeled molecules, such as [1-13C] pyruvate. This increased sensitivity enables detection of pyruvate conversion to lactate, as well as bicarbonate as surrogate markers of metabolism. Therefore, we hypothesize that HP-MRI will enable non-invasive detection of BAT activation, due to exercise and exerkine exposure. In Aim 1, we longitudinally track BAT activation in a mouse model of exercise using HP-MRI. We pioneer the development of two different HP imaging probes, [1-13C] pyruvate and diethyl-[1-13C]-α-ketoglutarate (DE--KG). We will then compare HP-MRI with gold-standard plasma exerkine measurements, to confirm metabolic activation. In Aim 2, we extend our experiments to use HP-MRI in offspring of exercised mice. Finally, we ask if HP-MRI can detect metabolic changes in offspring challenged with high-fat, high-fructose diets. Taken together, our Aims provide conceptual and technical innovation, pioneering a non-invasive imaging method to study the effects of exercise in pregnant mothers and their offspring. To ensure success, our research team consists of a unique combination of expertise in biochemistry, imaging, and exercise biology. Successful completion of the aims will have a major impact on our understanding of the long term effects of exercise, in both pregnant mothers and their offspring, well into adulthood.