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, And Douglas Burrin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

We aimed to characterize the lipidomic, metabolomic, and transcriptomic profiles in preterm piglets administered enteral (ENT) formula or three parenteral lipid emulsions [parenteral nutrition (PN)], Intralipid (IL), Omegaven (OV), or SMOFlipid (SL), for 14 days. Piglets in all parenteral lipid groups showed differential organ growth versus ENT piglets; whole body growth rate was lowest in IL piglets, yet there were no differences in either energy expenditure or13 C-palmitate oxidation. Plasma homeostatic model assessment of insulin resistance demonstrated insulin resistance in IL, but not OV or SL, compared with ENT. The fatty acid and acyl-CoA content of the liver, muscle, brain, and plasma fatty acids reflected the composition of the dietary lipids administered. Free carnitine and acylcarnitine (ACT) levels were markedly reduced in the PN groups compared with ENT piglets. 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. Our results show that new generation lipid emulsions directly enrich tissue fatty acids, especially in the brain, and lead to improved growth and insulin sensitivity compared with a soybean lipid emulsion. In all total PN groups, carnitine levels are limiting to the formation of ACTs and gene expression reflects the stress of excess lipid on liver function.-Guthrie, G., M. Kulkarni, H. Vlaardingerbroek, B. Stoll, K. Ng, C. Martin, J. Belmont, D. Hadsell, W. Heird, C. B. Newgard, O. Olutoye, J. van Goudoever, C. Lauridsen, X. He, E. H. Schuchman, and D. Burrin. Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions. J. Lipid Res.

Original languageEnglish
Pages (from-to)1696-1711
Number of pages16
JournalJournal of Lipid Research
Volume57
Issue number9
DOIs
StatePublished - Sep 2016
Externally publishedYes

Keywords

  • Fish oil
  • Lipidomics
  • Medium-chain triglycerides
  • Metabolomics
  • Parenteral nutrition-associated liver disease
  • Soybean oil
  • Total parenteral nutrition
  • Transcriptomics
  • Vitamin E

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