Project Summary
Obesity in pregnancy increases the risk for excessive adiposity in offspring, which tracks into adulthood and
can perpetuate across generations. Our preliminary data and published studies indicate that exercise initiated
during pregnancy in sedentary women with obesity lowers infant BMI z-scores and body fat percentage. These
benefits to infant health are more profound with resistance exercise during pregnancy. However, there are few
mechanistic studies in humans aimed at discerning mechanisms of maternal exercise-induced changes to
infant cellular metabolism. Our findings support the use of infant umbilical cord-derived mesenchymal stem
cells (MSCs) as a model to explore offspring cellular phenotypes in humans. Importantly, these MSCs are of
the same lineage that derive postnatal tissues and thus, can be differentiated into mesodermal cell types
important for regulating whole-body metabolism, such as myocytes and adipocytes. We have evidence of
improved cellular phenotype in infant MSCs exposed to maternal aerobic exercise (AE) with the greatest
improvements in MSC metabolism from maternal resistance exercise (RE). The objective of the proposed
study is to determine if maternal exercise mitigates the adverse consequences of gestational obesity exposure
using the MSC model in an ancillary study from a parent grant that is randomizing pregnant women with
obesity to AE, RE, or usual care control. A secondary objective is to determine if the MSC metabolic profiles
are associated with infant whole-body health outcomes at 1-, 6-, and 12-months of age. We will test this
hypothesis in 64 subjects from the parent trial. In Aim 1, we will determine the impact of maternal exercise in
women with obesity on infant MSC substrate metabolism and bioenergetic efficiency. These data will be
associated with infant whole-body resting energy expenditure and substrate oxidation via indirect calorimetry
over the first year of life. In Aim 2, we will determine the role of maternal exercise mode in women with obesity
on infant MSC adipogenesis and lipid storage. These data will be associated with infant body composition as
measured by DXA over the first year of life. In Aim 3, MSCs will undergo a multiomics approach where we will
identify candidate genes and epigenetic signatures of maternal exercise mode. These outcomes will be
correlated with blood metabolomic measures in the infant to establish gene-metabolite pathways. Leveraging a
large, rigorous RCT in pregnant women with obesity, this will be the first study to identify how maternal
exercise affects offspring cellular metabolism. This work will have significant impact by translating infant
cellular metabolic data with whole-body metabolic data across the first year of life.
