Polina Krassovskaia, Nicholas T. Broskey. East Carolina University, Greenville, NC.

BACKGROUND: Ectopic lipid in skeletal muscle (SM) has been linked to insulin resistance in individuals with metabolic diseases. The “Athlete’s Paradox” describes that individuals with metabolic diseases have high intramyocellular lipid content, which is associated with low insulin sensitivity, but athletes have a similarly high intramyocellular lipid content and high insulin sensitivity. Thus, exercise training increases the oxidative capacity of SM via increased oxidation of intramyocellular lipids concomitant with improvements in insulin sensitivity. Exercise during pregnancy as a mode of transferring the benefits of exercise to the developing fetus has gained traction and offers promising results to combat metabolic derangements in rodent models; however, it is not certain if these benefits can be translated to humans. Umbilical cord-derived mesenchymal stem cells (MSCs) are of fetal origin and are precursors to the satellite cell niche of SM in infants. Thus, MSCs can be used as an in vitro model for infant cellular metabolism. Closer insight into the programming of offspring metabolic tissue would allow for a better understanding of the benefit that maternal exercise has on offspring health and may provide a potential early target for combating metabolic disease risk. The purpose of this study will be to determine if the “Athlete’s Paradox” phenotype is retained in offspring of women who exercised during pregnancy. METHODS: Undifferentiated MSCs from women with obesity and gestational diabetes (GDM) will be cultured and compared to MSCs of women who are lean or exercised during pregnancy. At confluency, Oil Red O will be used to stain for lipid content. Radiolabeled glucose will be used to measure glycogen synthesis in the presence or absence of insulin as an index of insulin sensitivity. Insulin signaling proteins in the MSCs will also be measured in the basal and insulin-stimulated state. Results will be analyzed using unpaired t-tests, one-way or two-way repeated measures ANOVA, where appropriate. Factors tested will be group and treatment differences (i.e., insulin). ANTICIPATED RESULTS: We hypothesize that MSCs from women who exercised during pregnancy will retain the “Athlete’s Paradox” phenotype and display higher lipid content and higher insulin sensitivity compared to MSCs from women metabolically impaired (obesity and GDM) in pregnancy.

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