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African Americans, when compared with Caucasians, display greater insulin resistance in skeletal muscle. Differences in substrate utilization have been proposed as a factor for this health disparity; however, it remains unknown how early these differences manifest. Using infant umbilical cord-derived mesenchymal stem cells, we tested for in vitro glucose and fatty acid oxidation differences. Myogenically differentiated MSCs from African American offspring display higher rates of glucose oxidation and incomplete fatty acid oxidation.

Although the development of chemoresistance is multifactorial, active chemotherapeutic efflux driven by upregulations in ATP binding cassette (ABC) transporters are commonplace. Chemotherapeutic efflux pumps, like ABCB1, couple drug efflux to ATP hydrolysis and thus potentially elevate cellular demand for ATP resynthesis. Elevations in both mitochondrial content and cellular respiration are common phenotypes accompanying many models of cancer cell chemoresistance, including those dependent on ABCB1. The present study set out to characterize potential mitochondrial remodeling commensurate with ABCB1-dependent chemoresistance, as well as investigate the impact of ABCB1 activity on mitochondrial respiratory kinetics. To do this, comprehensive bioenergetic phenotyping was performed across ABCB1-dependent chemoresistant cell models and compared to chemosensitive controls. In doxorubicin (DOX) resistant ovarian cancer cells, the combination of both increased mitochondrial content and enhanced respiratory complex I (CI) boosted intrinsic oxidative phosphorylation (OXPHOS) power output. With respect to ABCB1, acute ABCB1 inhibition partially normalized intact basal mitochondrial respiration between chemosensitive and chemoresistant cells, suggesting that active ABCB1 contributes to mitochondrial remodeling in favor of enhanced OXPHOS. Interestingly, while enhanced OXPHOS power output supported ABCB1 drug efflux when DOX was present, in the absence of chemotherapeutic stress, enhanced OXPHOS power output was associated with reduced tumorigenicity.

Context Recent preclinical data suggest 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 and 35 years of age and ≤ 16 weeks’ gestation. Intervention Mothers were randomized into 1 of 2 groups: aerobic exercise (AE, n = 10) or nonexercise control (CTRL, n = 10). The AE group completed 150 minutes of weekly moderate-intensity exercise, according to American College of Sports Medicine guidelines, during pregnancy, whereas 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 nonoxidized glucose metabolite (NOGM) production (P ≤ 0.05). At D21, AE-MSCs had a significant elevation in glucose partitioning toward oxidation (oxidation/NOGM ratio) compared with CTRL (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 AE during pregnancy.

The birth rates among women of advanced maternal age (AMA) have risen over the last two decades; yet, pregnancies with AMA are considered high-risk and are associated with a significant increase in pregnancy complications. Although the mechanisms leading to pregnancy complications in women with AMA are not fully understood, it has been well established in the literature that offspring exposed to unfavorable environmental conditions in utero, such as gestational diabetes, preeclampsia, and/or intrauterine growth restriction during the early stages of development are subject to long-term health consequences. Additionally, angiogenic growth mediators, which drive vascular development of the placenta, are imbalanced in pregnancies with AMA. These same imbalances also occur in pregnancies complicated by preeclampsia, gestational diabetes, and obesity. This review discusses the impact of AMA on pregnancy and offspring health, and the potential mechanistic role of placental angiogenic growth mediators in the development of pregnancy complications at AMA.