Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs

Authors: GUTHRIE, GREGORY - Children'S Nutrition Research Center (CNRC); KULKARNI, MADHULIKA - Baylor College Of Medicine; VLAARDINGERBROEK, HESTER - Sophia Children'S Hospital; STOLL, BARBARA - Children'S Nutrition Research Center (CNRC); NG, KENNETH - Children'S Nutrition Research Center (CNRC); MARTIN, CAMILIA - Harvard Medical School; BELMONT, JOHN - Children'S Nutrition Research Center (CNRC); HADSELL, DARRYL - Children'S Nutrition Research Center (CNRC); HEIRD, WILLIAM - Children'S Nutrition Research Center (CNRC); NEWGARD, CHRIS - Duke University; OLUTOYE, OLUYINKA - Texas Children'S Hospital; VAN GOUDOEVER, JOHANNES - University Of Amsterdam; LAURIDSEN, CHARLOTTE - Aarhus University; SCHUCHMAN, EDWARD - The Icahn School Of Medicine At Mount Sinai; Burrin, Douglas - Doug

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/26/2016
Publication Date: 7/29/2016
Publication URL: http://handle.nal.usda.gov/10113/63052
Citation: Guthrie, G., Kulkarni, M., Vlaardingerbroek, H., Stoll, B., Ng, K., Martin, C., Belmont, J., Hadsell, D.L., Heird, W., Newgard, C., Olutoye, O., Van Goudoever, J., Lauridsen, C., Schuchman, E., Burrin, D.G. 2016. Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs. Journal of Lipid Research. 57(8):1-18. doi:10.1194/jlr.M069526.

Interpretive Summary: Preterm infants that are unable to be fed by mouth for an extended period of time are given nutrition intravenously consisting of amino acids, glucose, fats, minerals, and vitamins, which is referred to as total parenteral nutrition (TPN). For the past 40 years, oil from soy has been the main source of fat used in TPN for preterm infants. Associated with this soy oil has been the development of parenteral nutrition associated liver disease (PNALD), a potentially life threating liver disease if allowed to progress. To deal with this issue, newer products that contain other sources of fat from fish oil, olive oil, and coconut oil have been developed. Our previous study has shown that fish oil alone or a combination of soy oil, coconut oil, olive oil, and fish oil prevent the development of PNALD. The reason these fats do not cause development of PNALD is unclear. To understand this reason, we used preterm piglets to model human infants and administered either a milk diet or TPN containing soy oil, fish oil, or a combination soy oil, fish oil, coconut oil, and olive oil for 14 days. Piglets receiving fish oil grew better than soy oil-only piglets and had better control of blood sugar levels. We found that tissue, especially the brain, had a similar fat composition as the composition of the oil administered. TPN, regardless of oil administered, was stressful to the liver compared to the milk fed piglets.

Technical Abstract: New generation lipid emulsions comprised of fish oil or blends of soybean/fish/medium chain triglyceride/olive oil are emerging that result in favorable clinical metabolic outcomes in pediatric populations. Our aim was to characterize the lipidodomic, metabolomic, and transcriptomic profiles these lipid emulsions in preterm piglets administered enteral formula (ENT) or 3 parenteral lipid emulsions, Intralipid (IL), Omegaven (OV), or SMOFlipid (SL), as part of complete PN for 14 d. Pigs in all PN groups showed differential organ growth vs ENT pigs and growth velocity was lowest in IL pigs, yet there were no differences in either whole body energy expenditure or (13)C-palmitate oxidation rates. Plasma HOMA-IR demonstrated insulin-resistance in IL, but not OV or SL, compared to ENT. The fatty acid and acyl-CoA content of the liver, muscle, and plasma fatty acids reflected the composition of the dietary lipids administered. Free carnitine and acyl-carnitine levels were markedly reduced in the PN groups compared to ENT pigs. Genes associated with oxidative stress and inflammation were increased, whereas, those associated with alternative pathways of fatty acid oxidation were decreased in all PN groups. We conclude that the lipid composition of emulsions directly effects tissue lipid content, whereas TPN carnitine levels are limiting to the formation of acylcarnitines. Also, gene expression of TPN piglets reflects the stress of excess lipid on liver function.