<i>In utero</i>chronic lipid exposure increases mid-gestation fetal cardiomyocyte lipid uptake<i>in vitro</i>

Fetal circulating fatty acids are typically low, and the fetal heart primarily relies on carbohydrates to meet energy demands. Preterm infants sometimes require parenteral nutrition, including Intralipid 20®, a lipid emulsion used to support growth and prevent essential fatty acid deficiency. While a critical intervention, lipid infusion at an early post-conceptional age exposes the developing heart to unexpectedly high levels of circulating fatty acids. The objective of this study was to understand how high circulating lipid concentrations at mid-gestation, a comparable age to preterm infants needing parenteral nutrition, affects cardiomyocyte lipid handling. We hypothesized that chronic exposure to high circulating lipid levels would promote cardiomyocyte maturation and increase capacity to uptake and process fatty acids. Fetal sheep from twin pregnancies were randomized and infused with either Intralipid 20® or Lactated Ringer’s Solution (control) for 8 days starting at gestational day 89±1. Fetuses were euthanized on gestational day 97±1 (term 147 days). Control N=8 (2 female, 6 male), Intralipid 20® N=9 (6 female, 3 male). All animal studies were performed at Oregon Health &amp; Science University and approved by the Institutional Animal Care and Use Committee (#IP0007). Lipid droplets were imaged in live, freshly isolated cardiomyocytes through the incorporation of exogenous fatty acids Bodipy C12 (LCFA, 18 carbon) and Bodipy C16 (VLCFA, 22 carbon) on the Zeiss LSM 880 with Airyscan microscope. Images were analyzed in ImageJ. In utero Intralipid 20® exposed cardiomyocytes had a more robust response to in vitro Bodipy-labeled lipids, culminating in significantly higher lipid droplet density of both LCFA (p=0.0282) and VLCFA (p=0.0054), and significantly larger VLCFA-containing lipid droplets (p=0.0305). Data were analyzed by 2-way ANOVA. Significant p-values reported are for treatment main effects; there was no main effect of sex. There was no interaction between sex and treatment. These changes indicate that lipid exposure can mature cardiomyocytes in mid-gestation. National Heart, Lung, and Blood Institute: R01HL146997 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.