Effects of maternal exercise on infant mesenchymal stem cell mitochondrial function, insulin action, and body composition in infancy.

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. 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. We found that infants from exercising mothers have improvements in MSC insulin signaling 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 leaner at 1 month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6 months of age. 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.

Effect of resveratrol on insulin action in primary myotubes from lean individuals and individuals with severe obesity.

Resveratrol, a natural polyphenol compound contained in numerous plants, has been proposed as a treatment for obesity-related disease processes such as insulin resistance. However, in humans there are conflicting results concerning the efficacy of resveratrol in improving insulin action; the purpose of the present study was to determine whether obesity status (lean, severely obese) affects the response to resveratrol in human skeletal muscle. Primary skeletal muscle cells were derived from biopsies obtained from age-matched lean and insulin-resistant women with severe obesity and incubated with resveratrol (1 µM) for 24 h. Insulin-stimulated glucose oxidation and incorporation into glycogen, insulin signal transduction, and energy-sensitive protein targets [AMP-activated protein kinase (AMPK), Sirt1, and PGC1α] were analyzed. Insulin-stimulated glycogen synthesis, glucose oxidation, and AMPK phosphorylation increased with resveratrol incubation compared with the nonresveratrol conditions (main treatment effect for resveratrol). Resveratrol further increased IRS1, Akt, and TBC1D4 insulin-stimulated phosphorylation and SIRT1 content in myotubes from lean women, but not in women with severe obesity. Resveratrol improves insulin action in primary human skeletal myotubes derived from lean women and women with severe obesity. In women with obesity, these improvements may be associated with enhanced AMPK phosphorylation with resveratrol treatment.NEW & NOTEWORTHY A physiologically relevant dose of resveratrol increases insulin-stimulated glucose oxidation and glycogen synthesis in myotubes from individuals with severe obesity. Furthermore, resveratrol improved insulin signal transduction in myotubes from lean individuals but not from individuals with obesity. Activation of AMPK plays a role in resveratrol-induced improvements in glucose metabolism in individuals with severe obesity.

Effects of Maternal Exercise Modes on Glucose and Lipid Metabolism in Offspring Stem Cells.

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, resistance (RE), or combination 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 acid(s) 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) toward 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 toward 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. Clinical Trial: ClinicalTrials.gov Identifier: NCT03838146.