Date of this Version
Low birthweight due to intrauterine growth restriction is associated with metabolic disorders after birth. Our 1st study assessed deficits in skeletal muscle glucose metabolism and pancreatic β cell function in IUGR fetal sheep. We aimed to evaluate the effectiveness of daily intravenous infusions of the anti-inflammatory ω-3 polyunsaturated fatty acid (PUFA), eicosapentaenoic acid (EPA), as a means of improving deficits previously observed in the IUGR fetus by targeting fetal systemic inflammation. The presence of systemic inflammation in IUGR fetuses was evident by increased total circulating populations of total leukocytes, lymphocytes, and monocytes. However, these were decreased by 5-day ω-3 PUFA infusions. Additional blood parameters including lactate and CO2 were increased in IUGR fetuses, regardless of infusion of EPA. Poor β cell function in IUGR fetuses was improved by EPA infusion, as evident by improved circulating plasma insulin, O2, CO2, HCO3, Na+, K+, and Cl- during a hyperglycemic clamp. Hindlimb glucose uptake and oxidation rates, which were impaired by IUGR were improved by EPA infusion as well. These findings indicate that targeting systemic fetal inflammation by infusion of the anti-inflammatory ω-3 PUFA, EPA, many IUGR-associated deficits in glucose metabolism and β cell function in the IUGR fetal sheep were resolved.
Our 2nd study sought to determine the effectiveness of daily EPA infusions on fetal growth biometrics and skeletal muscle-specific deficits associated with IUGR. In IUGR fetuses, decrease in mass were observed for whole fetus, hindlimb, semitendinosus, soleus, longissimus dorsi, lungs, and kidneys, but 5-day EPA infusion improved most of these deficits. The fiber type ratios of skeletal muscle estimated by myosin heavy chain proportions were also altered by IUGR but were recovered by EPA infusion as well. Ex vivo glucose uptake and oxidation capacities were impaired in IUGR muscle but were improved after daily EPA infusions. Results from this study indicate that daily fetal ω-3 PUFA infusions of EPA were effective in improving fetal growth biometrics, body composition, and muscle-specific glucose metabolism.
Advisor: Dustin T. Yates