339 - Comparison of two parenteral lipid emulsions and their effects on hepatic DNA methylation in newborns guinea pigs

Abstract

Background Parenteral nutrition (PN) is necessary for preterm infants unable to receive enteral nutrition. However, PN is contaminated by peroxides inducing oxidative stress, which is known to modify the enzymes involved in DNA methylation. Therefore, alteration of DNA methylation is suspected in infants on PN. Among PN ingredients, lipid emulsion is an important source of oxidants. Because of differences in their content – higher vitamin E and lower omega-6 PUFA in SMOF- we hypothesize that DNA methylation differs whether PN is compounded with Intralipid (IL) or SMOFLipid (SMOF). Objective Assess the impact of PN containing IL or SMOF, on redox potential of glutathione, S-adenosylmethionine (SAM), methylcytosine (5-MedCyd), methionine adenosyltransferase (MAT) and DNA methyltransferases (DNMT) in newborn animals. Methods 3-day-old guinea pigs were randomized into 3 groups: IL: infused with total PN containing IL as lipid emulsion; SMOF: infused with total PN containing SMOF as lipid emulsion; and Control: orally fed. Redox potential, SAM, 5-MedCyd, MAT and DNMTs activity were quantified in the liver after 4 days of experiment. Statistics: ANOVA, p Results PN groups were more oxidized (-210±2 > -228±1 mV) and presented higher rates of 5-MedCyd (8.2±0.5 >5.6±0.9 pmol/μg DNA), SAM (22.2±1.4 > 14±2) and increased activity of DNMTs (524.6±69 > 274.3±50) compared to control. 5-MedCyd rates was more increased in SMOF than IL. Redox potential was associated with global DNA hypermethylation (R2 = 0.55 p 19±1 nmol/g tissue). Conclusion PN changes the hepatic redox potential leading to modifications in DNA methylation metabolism. SMOF exhibits more pronounced effects compare to IL, suggesting a cautious before using SMOF as an alternative to IL in PN. Further analyses are required to explore the molecular mechanisms caused by the different components such as fatty acids on DNA methylation.