Influence of Maternal Exercise on Glucose and Lipid Metabolism in Offspring Stem Cells: ENHANCED by Mom

Abstract

Context Recent preclinical data suggests exercise during pregnancy can improve the metabolic phenotype not only of the mother, but of the developing offspring as well. However, investigations in human offspring are lacking. Objective To characterize the effect of maternal aerobic exercise on the metabolic phenotype of the offspring’s mesenchymal stem cells (MSCs). Design Randomized controlled trial. Setting Clinical research facility. Patients Healthy female adults between 18-35 years of age and ≤16 weeks’ gestation. Intervention Mothers were randomized into one of two groups: aerobic exercise (AE, n=10) or non-exercise control (CON, n=10). The AE group completed 150 min of weekly moderate-intensity exercise, according to ACSM guidelines, during pregnancy while controls attended stretching sessions. Main Outcome Measures Following delivery, MSCs were isolated from the umbilical cord of the offspring and metabolic tracer and immunoblotting experiments were completed in the undifferentiated (D0) or myogenically differentiated (D21) state. Results AE-MSCs at D0 had an elevated fold-change over basal in insulin-stimulated glycogen synthesis and reduced non-oxidized glucose metabolite (NOGM) production (p≤0.05). At D21, AE-MSCs had a significant elevation in glucose partitioning toward oxidation (oxidation/NOGM ratio) compared to CON (p≤0.05). Immunoblot analysis revealed elevated complex I expression in the AE-MSCs at D21 (p≤0.05). Basal and palmitate-stimulated lipid metabolism was similar between groups at D0 and D21. Conclusions These data provide evidence of a programmed metabolic phenotype in human offspring with maternal aerobic exercise during pregnancy.

Influence of Maternal Exercise on Maternal and Offspring Metabolic Outcomes

“…Maternal blood lipids are associated with infant adiposity and alterations in MSC metabolism in offspring from mothers with obesity [63,64,78] suggesting a potential in-utero influence of maternal lipids on fetal metabolic programing. Recently shown, maternal aerobic exercise during gestation may alter the MSC phenotype, however, improvements in lipid oxidation, oxidation efficiency or uptake, and accumulation were not significant [83]. While the lack of effect is surprising based on previously described effects in rodent models and MSCs from offspring of mothers with obesity, it must be noted that exercising mothers were seemingly healthy and thus potentially "diluting" the effect of maternal exercise on offspring metabolic reprograming.…”

“…Evidence for maternal dysglycemia altering offspring metabolism can be further observed at the level of MSCs where metabolic derangements coincide with derangements in maternal glycemic control (i.e., HOMA-IR) [64]. Further, maternal aerobic exercise increases insulin-mediated glycogen synthesis rates in undifferentiated MSCs suggestive of greater insulin sensitivity [83]. This effect was paralleled with greater insulin-mediated phosphorylation of signaling marker GSK-3β in undifferentiated MSCs.…”

“…In addition to glycogen synthesis, enhanced glucose oxidation efficiency and partitioning of glucose towards oxidation is observed in both undifferentiated and myogenically differentiated MSCs from offspring of aerobically trained mothers. Interestingly, a trend towards a greater capacity for glucose oxidation was observed in myogenically differentiated but not undifferentiated MSCs [83]. It is worth noting that there is greater expression of complex I in myogenically differentiated MSCs, which could in part influence the greater glucose oxidation rates considering that glucose oxidation increases the input of electrons to complex I of mitochondria [83]; however, this effect needs to be further elucidated.…”

“…Interestingly, a trend towards a greater capacity for glucose oxidation was observed in myogenically differentiated but not undifferentiated MSCs [83]. It is worth noting that there is greater expression of complex I in myogenically differentiated MSCs, which could in part influence the greater glucose oxidation rates considering that glucose oxidation increases the input of electrons to complex I of mitochondria [83]; however, this effect needs to be further elucidated. As previously described, obesity driven metabolic derangements lead to less efficient mitochondria with a lower oxidative capacity; thus, it is possible that a greater capacity to oxidize glucose may attenuate the transmission of decrements in glucose metabolism across generations.…”

“…While the lack of effect is surprising based on previously described effects in rodent models and MSCs from offspring of mothers with obesity, it must be noted that exercising mothers were seemingly healthy and thus potentially "diluting" the effect of maternal exercise on offspring metabolic reprograming. Accordingly, the positive effects of maternal exercise on offspring MSC lipid metabolism may be pronounced in situations where an adverse intrauterine environment is instilled by maternal metabolic disease (i.e., obesity) [63][64][65]83]; however, there are currently no studies exploring these effects.…”