Context Maternal exercise positively influences pregnancy outcomes and metabolic health in progeny; however, data regarding the effects of different modes of prenatal exercise on offspring metabolic phenotype is lacking. Objective To elucidate the effects of different modes of maternal exercise on offspring umbilical cord derived mesenchymal stem cell (MSC) metabolism. Design Randomized controlled trial. Setting Clinical research facility. Patients Healthy females between 18 and 35 years of age and <16 weeks’ gestation. Intervention Women were randomized to either 150-minutes of moderate intensity aerobic (AE), resistance (RE) or combination (CE) exercise per week, or to a non-exercising control. Main Outcome Measures At delivery, MSCs were isolated from the umbilical cords. MSC glucose and fatty metabolism was assessed using radiolabeled substrates. Results MSCs from offspring of all the exercising women demonstrated greater partitioning of oleate (p=≤0.05) and palmitate (p=≤0.05) towards complete oxidation, relative to non-exercisers. MSCs from offspring of all exercising mothers also had lower rates of incomplete fatty acid oxidation (p=≤0.05), which was related to infant adiposity at 1-month of age. MSCs from all exercising groups exhibited higher insulin-stimulated glycogen synthesis rates (p=≤0.05), with RE having the largest effect (p=≤0.05). RE also had the greatest effect on MSC glucose oxidation rates (p=≤0.05) and partitioning towards complete oxidation (p=≤0.05). Conclusion Our data demonstrates that maternal exercise enhances glucose and lipid metabolism of offspring MSCs. Improvements in MSC glucose metabolism seem to be the greatest with maternal RE.
Next-generation sequencing has resulted in an explosion of available data, much of which remains unstudied in terms of biochemical function; yet, experimental characterization of these sequences has the potential to provide unprecedented insight into the evolution of enzyme activity. One way to make inroads into the experimental study of the voluminous data available is to engage students by integrating teaching and research in a college classroom such that eventually hundreds or thousands of enzymes may be characterized. In this study, we capitalize on this potential to focus on SABATH methyltransferase enzymes that have been shown to methylate the important plant hormone, salicylic acid (SA), to form methyl salicylate. We analyze data from 76 enzymes of flowering plant species in 23 orders and 41 families to investigate how widely conserved substrate preference is for salicylic acid methyltransferase (SAMT) orthologs. We find a high degree of conservation of substrate preference for SA over the structurally similar metabolite, benzoic acid, with recent switches that appear to be associated with gene duplication and at least three cases of functional compensation by paralogous enzymes. The presence of Met in active site position 150 is a useful predictor of SA methylation preference in SABATH methyltransferases but enzymes with other residues in the homologous position show the same substrate preference. Although our dense and systematic sampling of SABATH enzymes across angiosperms has revealed novel insights, this is merely the “tip of the iceberg” since thousands of sequences remain uncharacterized in this enzyme family alone.
Epigenetic transmission of metabolic disease to an offspring increases their risk for development of metabolic disease later in life. With the increasing rates of obesity in women of child-bearing age it is critical to develop strategies to prevent perpetuating metabolic disease across generations. Maternal exercise during gestation imprints offspring metabolic phenotype, thus increasing their imperviousness to metabolic assaults later in life. In rodent models, maternal exercise before and during gestation leads to enhanced offspring glycemic control, mitochondrial bioenergetics, and lower adiposity, which decreases their risk for development of future metabolic disease. In humans, maternal gestational exercise decreases pregnancy complications and improves maternal and offspring metabolism on both the whole-body and the cellular level. Maternal exercise restores the obesity-induced metabolic derangements, restoring maternal and offspring metabolic phenotype. While unknown, different exercise modalities might have a differential effect, however, evidence remains scarce.
ObjectiveIn adults, skeletal muscle insulin sensitivity (SI) and fatty acid oxidation (FAO) are linked with a predisposition to obesity. The current study aimed to determine the effects of maternal exercise on a model of infant skeletal muscle tissue (differentiated umbilical cord mesenchymal stem cells [MSCs]) SI and FAO and analyzed for associations with infant body composition.MethodsFemales <16 weeks' gestation were randomized to either 150 min/wk of moderate‐intensity aerobic, resistance, or combination exercise or a nonexercising control. At delivery, MSCs were isolated from umbilical cords and myogenically differentiated, and SI and FAO were measured using radiolabeled substrates. Infant body fat percentage (BF%) and fat‐free mass were calculated using standard equations at 1 and 6 months of age.ResultsMSCs from infants of all exercisers had significantly (p < 0.05) higher SI. MSC SI was inversely associated with infant BF% at 1 (r = −0.38, p < 0.05) and 6 (r = −0.65, p < 0.01) months of age. Infants with high SI had lower BF% at 1 (p = 0.06) and 6 (p < 0.01) months of age. MSCs in the high SI group had higher (p < 0.05) FAO.ConclusionsExposure to any type of exercise in utero improves offspring SI and could reduce adiposity in early infancy.
Type 2 diabetes is more prevalent in African American (AA) than Caucasian (C) adults. Further, differential substrate utilization has been observed between AA and C adults, but data regarding metabolic differences between races at birth remains scarce. The purpose of the present study was to determine if there are racial differences in substrate metabolism evident at birth utilizing mesenchymal stem cells (MSCs) collected from offspring umbilical cords. Using radio-labeled tracers, MSCs from offspring of AA and C mothers were tested for glucose and fatty acid metabolism in the undifferentiated state and while undergoing myogenesis in vitro. Undifferentiated MSCs from AA exhibited greater partitioning of glucose towards non-oxidized glucose metabolites. In the myogenic state, AA displayed higher glucose oxidation, but similar fatty acid oxidation rates. In the presence of both glucose and palmitate, but not palmitate only, AA exhibit a higher rate of incomplete fatty acid oxidation evident by a greater production of acid soluble metabolites. Myogenic differentiation of MSCs elicited an increase in glucose oxidation in AA, but not in C. Together, these data suggest that metabolic differences between AA and C races may exist at birth.
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