3 Metabolic response to premature lipid exposure in fetal cardiomyocytes

Abstract Abstract: Introduction Fetal plasma lipid concentrations are low, and cardiomyocytes rely on carbohydrates as their primary fuel source. Circulating lipid levels may be prematurely elevated by maternal dyslipidemia or parenteral nutrition in preterm neonates. In late-term fetal sheep, maximal respiration was lower in cardiomyocytes exposed to Intralipid infusion compared to Controls. It is unclear whether fetal cardiomyocyte metabolism is altered by Intralipid exposure during mid-gestation. Objective Test the hypothesis that maximal oxygen consumption rate (OCR) is lower in cardiomyocytes from mid-gestation fetal sheep exposed to 8-day Intralipid treatment compared to fetuses receiving vehicle infusion in utero. Methods Mid-gestation fetal sheep received Intralipid 20® or vehicle infusion from 89 to 97 days of gestation. Left ventricular cardiomyocytes were isolated and cultured. Maximal OCR was measured in cardiomyocytes with or without additional exposure to palmitic acid in vitro. Results There was a significant interaction among fetal sex and in vivo Intralipid treatment for maximal OCR in cardiomyocytes cultured in standard media (P=0.018); OCR was 30% lower in males receiving Intralipid treatment compared to male Controls (P=0.037). Maximal OCR was similar between Control and Intralipid cardiomyocytes exposed to palmitic acid in vitro. Conclusion These findings indicate that mid-gestation Intralipid treatment reduces cardiomyocyte OCR in a sex-dependent manner. Similarities between Control and Intralipid cardiomyocytes treated with palmitic acid in vitro suggest that the metabolic response to lipid substrate is not compounded by prior lipid exposure. (Supported by NIH R01HL146997)