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Title: Hepatic transcriptomic profiles of preterm piglets nourished by enteral and parenteral nutrition

item KULKARNI, MADHULIKA - Children'S Nutrition Research Center (CNRC)
item VLAARDINGERBROEK, HESTER - Sophia Children'S Hospital
item BELMONT, JOHN - Children'S Nutrition Research Center (CNRC)
item HADSELL, DARRYL - Children'S Nutrition Research Center (CNRC)
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item OLUTOYE, OLUYINKA - Children'S Nutrition Research Center (CNRC)
item VAN GOUDOEVER, JOHANNES - University Of Amsterdam
item Burrin, Douglas - Doug

Submitted to: Pediatric Research
Publication Type: Abstract Only
Publication Acceptance Date: 4/11/2013
Publication Date: 5/4/2013
Citation: Kulkarni, M., Vlaardingerbroek, H., Belmont, J.W., Hadsell, D.L., Stoll, B., Olutoye, O., Van Goudoever, J.B., Burrin, D.G. 2013. Hepatic transcriptomic profiles of preterm piglets nourished by enteral and parenteral nutrition [abstract]. Pediatric Research. E-PAS213:4170.5.

Interpretive Summary:

Technical Abstract: Parenteral nutrition is a life-saving nutritional support for more than half a million premature and hospitalized infants in the U.S. annually. Lipids in parenteral nutrition provide essential fatty acids and are a major source of energy. Intralipid (IL) is the only approved lipid emulsion in the U.S., yet new generation emulsions are emerging with different fatty acid composition, including Omegaven (OV) and SMOFlipid (SL). The objective of this study was to compare the gene expression data in the liver tissue of enterally fed piglets to the TPN-fed groups and among different lipid emulsions. Preterm pigs were assigned to 4 groups (7-14 pigs per group; equal daily macronutrient intake with 5 g per kg lipid): PN+IL, PN+OV, PN+SL, and an enteral group fed milk formula (EN). Liver tissue was collected after 14 d and RNA extracted. RNAseq (50 bp single read) was performed on an Illumina HiSeq2000 using standard protocols for library construction and sequencing. RNAseq data was analyzed by using the Bowtie2 suite to align and count normalized transcript abundance. Cuffdiff was used to generate lists of differentially expressed and spliced transcripts. These lists of differentially expressed genes were then subjected to ingenuity pathway analysis (IPA). As a result, Cuffdiff analysis detected significant differences in 126 genes between IL vs EN, 113 in OV vs EN, and 17 in SMOF vs EN. IPA of IL vs EN showed that the most significantly altered pathways of molecular and cellular functions were lipid metabolism and molecular transport. Canonical pathway analysis of IL vs EN showed overrepresentation of NRF-2-mediated oxidative stress response mediated by genes including Jun, Ras, HSP, FMO1, SOD, HERPUD1, and AOX1 and of the LXR/RXR pathway involving apoA4 affecting the cholesterol efflux. Also, there was overrepresentation of clarithrin mediated endocytosis signaling and acute phase response signaling. Similar patterns were found in comparison of OV and SMOF vs. EN. A notable difference was the overrepresentation of IL17A in OV mediated by S100A9 and CCL20 and in SMOF mediated by lipocalin 2. In conclusion, our genome-wide, transcriptomic analysis of liver tissue in preterm piglets provides insight into complex pathways involved in the metabolism in parenteral vs enteral nutrition and emphasizes the activation of oxidative stress and acute phase responses with TPN.