Objective: Rates of pediatric obesity are continuously rising and are likely to translate into a high incidence of metabolic disease later in life. Maternal exercise (ME) has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to infant tissues (e.g., skeletal muscle), and remain involved in mature tissue maintenance. Importantly, these cells maintain metabolic characteristics of an offspring donor and provide a model for the investigation of mechanisms behind infant metabolic health improvements. Methods: We used undifferentiated MSC to investigate if ME affects infant MSC mitochondrial function and insulin action, and if these adaptations are associated with lower infant adiposity. Results: We found that infants from exercising mothers have improvements in MSC insulin signaling are related to higher MSC respiration and fat oxidation, and expression and activation of energy-sensing and redox-sensitive proteins. Further, we found that infants exposed to exercise in utero were seemingly leaner at 1-month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6-months of age. Conclusion: These data suggest that infants from exercising mothers are relatively leaner and this is associated with higher infant MSC mitochondrial respiration, fat use, and insulin action.

The authors have declared no competing interest.

NCT03838146

This project was supported by the American Heart Association (18IPA34150006 to L.E.M.)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Approval for this study and all experiments was obtained from the East Carolina University Review Board (IRB#: 12-002524).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data generated/analyzed during the current study is available upon request from the corresponding or lead author.