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Multi-Omic Profiles of Hepatic Metabolism in TPN-fed Preterm Pigs Administered New Generation Lipid Emulsions

Gregory Guthrie, Madhulika Kulkarni, Hester Vlaardingerbroek, Barbara Stoll, Kenneth Ng, Camilia Martin, John Belmont, Darryl Hadsell, William Heird, Christopher B. Newgard, Oluyinka Olutoye, Johannes van Goudoever, Charlotte Lauridsen, Xingxuan He, Edward H. Schuchman, Douglas Burrin
Journal of lipid research 2016 v.57 pp. 1696-1711
acyl coenzyme A, beta oxidation, carnitine, dietary fat, emulsions, energy expenditure, fatty acids, fish, fish oils, gene expression, genes, inflammation, insulin resistance, lipid content, liver, liver function, metabolomics, muscles, olive oil, oxidation, oxidative stress, palmitates, piglets, soybeans, transcriptomics, triacylglycerols
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.