Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions

• Published in: Journal of lipid research Vol. 57; no. 9; pp. 1696 - 1711
• Main Authors: Guthrie, Gregory, Kulkarni, Madhulika, Vlaardingerbroek, Hester, Stoll, Barbara, Ng, Kenneth, Martin, Camilia, Belmont, John, Hadsell, Darryl, Heird, William, Newgard, Christopher B., Olutoye, Oluyinka, van Goudoever, Johannes, Lauridsen, Charlotte, He, Xingxuan, Schuchman, Edward H., Burrin, Douglas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2016; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Animals; Animals, Newborn - growth & development; Animals, Newborn - metabolism; Dietary Fats, Unsaturated - administration & dosage; Emulsions - administration & dosage; Fatty Acids - metabolism; fish oil; Fish Oils - administration & dosage; Lipid Metabolism - genetics; lipidomics; Liver - drug effects; Liver - metabolism; Male; medium-chain triglycerides; metabolomics; Palmitic Acid - administration & dosage; Palmitic Acid - metabolism; Parenteral Nutrition; parenteral nutrition-associated liver disease; Phospholipids - administration & dosage; soybean oil; Soybean Oil - administration & dosage; Swine - growth & development; Swine - metabolism; total parenteral nutrition; transcriptomics; Triglycerides - metabolism; vitamin E; metabolomics; parenteral nutrition-associated liver disease; total parenteral nutrition; soybean oil; fish oil; vitamin E; medium-chain triglycerides; transcriptomics; lipidomics
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M069526

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 or 13C-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.