Nicholas T. Broskey

This study revealed that maternal metabolic flexibility—the ability to switch between fuel sources depending on availability—and greater reliance on lipid oxidation during fasting in late pregnancy were linked to higher infant birth weight and adiposity, independent of gestational weight gain. These findings suggest that maternal substrate oxidation influences fetal nutrient supply and, consequently, growth, thereby playing a key role in shaping neonatal body composition and long-term health outcomes.

Purpose: Exercise-mediated adaptations to mitochondria are well established in non-gravid populations; however, the extent to which these adaptations occur during pregnancy remains unclear. Therefore, the objective of this study was to compare skeletal muscle mitochondrial bioenergetics in physically Active (A, n=10) versus Sedentary (S, n=9) pregnant women. Methods: Groups were matched for age, race, and pre-gravid BMI and were studied in the second (T2; weeks 21-25) and third trimester (T3; weeks 31-35). Free-living physical activity was assessed by accelerometry and aerobic fitness by VO2peak testing. In vivo mitochondrial capacity was assessed by 31P-magnetic resonance spectroscopy. Primary skeletal muscle myotubes were obtained via muscle biopsy between late T2 and early T3. Mitochondrial in vitro respiration was assessed by high-resolution respirometry, and mitochondrial content was measured by Western blot and enzyme activity. Results: Despite a decline in physical activity across gestation, A maintained a higher VO2peak at T2 (p<0.05) and T3 (p<0.01) compared to S. There were no differences in PCr recovery time between groups or timepoints. Myotube mitochondrial respiratory capacity was similar between groups; however, compared to S, A demonstrated increased expression of mitochondrial complexes I, II, and IV (all p<0.05) proteins. Additionally, myotube mitochondrial efficiency (ATP/O ratio) measures positively correlated with maternal VO2peak at T3 (r=0.49, p<0.05), suggesting a link between fitness and mitochondrial efficiency. Conclusions: These findings suggest that late pregnancy may blunt mitochondrial adaptations to aerobic exercise despite a preservation of cardiovascular fitness. Future studies are needed to determine whether increasing activity throughout gestation can enhance mitochondrial respiration.

This study was the first to test how specific prenatal exercise dose, i.e., the FITT-V (frequency, intensity, time, type, volume) metrics, could influence the storage of triglycerides in infant adipogenic mesenchymal stem cells (MSCs). Prenatal exercise led to a reduction in infant whole body fat percentage (BF%), which was reflected by lower lipid storage in infant MSCs. Changes in lipid content were observed in offspring born to participants exercising beyond the minimum recommended weekly volume, 450 metabolic equivalent (MET)·min/wk.

Summary: Skeletal muscle (SkM) insulin resistance is a central defect in T2D, yet cell specific molecular determinants remain incompletely understood. Here, we integrate full-length single-nucleus transcriptomics with gold-standard stable isotope-labeled hyperinsulinemic-euglycemic clamps to generate a nucleus-resolved transcriptomic atlas of SkM insulin resistance. We identify previously unrecognized myonuclear populations whose proportions associate with insulin sensitivity across independent cohorts, revealing MYH7B+ myonuclei are metabolically favorable over EGF+ myonuclei. Modeling transcriptional variation against tracer-derived glucose disposal uncovers highly nucleus-specific molecular programs that are obscured when using surrogate fasting indices. Mechanistically, we identify zinc transporter ZIP14 as a positive regulator of insulin-stimulated glucose uptake and implicate EGF signaling in impaired branched-chain amino acid catabolism and inflammatory cross-talk within the SkM niche. Together, these findings redefine SkM insulin resistance as a multicellular, nucleus-resolved process and highlight new cell type specific targets for metabolic intervention.

Mesenchymal stem cells (MSCs) of infants born to women with gestational diabetes mellitus (GDM) treated by metformin display lower rates of oleate oxidation despite no limitations in lipid availability compared with GDM treated by diet. Mitochondrial capacity was also lower among infant MSCs from metformin-treated GDM.

Maternal resistance exercise increases infant energy expenditure. This increase creates a gap between the measured and estimated energy expenditure when using standard estimation equations. These findings suggest that maternal resistance exercise can serve as a nonpharmacological method to enhance an infant’s daily caloric expenditure.

Paternal obesity decreases infant mesenchymal stem cell (MSC) basal and maximal respiration. Lower OXPHOS and electron transport system capacity could be explained by lower complex I and IV respiratory capacity but not changes in OXPHOS expression in infant MSC from fathers with obesity. Paternal obesity and altered MSC mitochondrial functional capacity are associated with a greater infant weight-to-length ratio at birth.

Maternal obesity is associated with lower infant resting energy expenditure (REE), predisposing them to more rapid weight and adiposity gain through early infancy. Maternal exercise (ME) decreases infant adiposity and risk for childhood obesity; however, it remains unknown if this is in part mediated by changes in infant energy expenditure. Thus, we measured REE in 1-month-old infants from pregnant individuals who performed moderate-intensity exercise during pregnancy and compared it to infants from non-exercising controls. We observed higher oxygen respiratory rates (p = 0.003 for VO₂ and p = 0.007 for VCO₂) and REE (p = 0.002) in infants exposed to exercise in utero, independent of any differences in infant body composition. Furthermore, maternal BMI was significantly and inversely associated with infant REE in the control (r = −0.86, R² = 0.74, p = 0.029), but not the exercise group (r = 0.33, R² = 0.11, p = 0.473). Together, these findings associate ME with increasing infant energy expenditure which could be protective of subsequent infant adiposity gain. Clinical Trial: ClinicalTrials.gov Identifier: NCT03838146 and NCT04805502.