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Effect of Maternal Exercise in Women with Obesity on Offspring Mesenchymal Stem Cell Metabolism

Award Number: R01DK137945
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/09/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Effect of Maternal Exercise in Women with Obesity on Offspring Mesenchymal Stem Cell Metabolism - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $552,661 )
2026	2026	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/15/2025	NON-COMPETING CONTINUATION	$552,661
														Subtotal = $552,661

Issue Date FY: 2025 ( Subtotal = $472,576 )
2025	2025	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/31/2024	NON-COMPETING CONTINUATION	$425,319
2025	2025	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/14/2025	NON-COMPETING CONTINUATION	$47,257
														Subtotal = $472,576

Issue Date FY: 2024 ( Subtotal = $472,418 )
2024	2024	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/9/2024	NEW	$472,418
														Subtotal = $472,418

Grand Total All Awards = $1,497,655

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Effect of Maternal Exercise in Women with Obesity on Offspring Mesenchymal Stem Cell Metabolism

Award Number: R01DK137945

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/09/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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