title: Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions.
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 or (13)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.
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Gregory
authors.initials: G
authors.lastname: Guthrie
authors.affiliation: Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kulkarni
authors.affiliation: Department of Pediatrics, Emma Children's Hospital-Academisch Medisch Centrum, Amsterdam, The Netherlands.
authors.forename: Hester
authors.initials: H
authors.lastname: Vlaardingerbroek
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Barbara
authors.initials: B
authors.lastname: Stoll
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ng
authors.affiliation: Department of Neonatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Camilia
authors.initials: C
authors.lastname: Martin
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: John
authors.initials: J
authors.lastname: Belmont
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Darryl
authors.initials: D
authors.lastname: Hadsell
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: William
authors.initials: W
authors.lastname: Heird
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Departments of Pharmacology and Cancer Biology and Medicine, Duke University, Durham, NC.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX.
authors.forename: Oluyinka
authors.initials: O
authors.lastname: Olutoye
authors.affiliation: Department of Pediatrics, Emma Children's Hospital-Academisch Medisch Centrum, Amsterdam, The Netherlands Department of Pediatrics, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: van Goudoever
authors.affiliation: Department of Animal Science, Aarhus University, Tjele, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lauridsen
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Xingxuan
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX doug.burrin@ars.usda.gov.
authors.forename: Douglas
authors.initials: D
authors.lastname: Burrin
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D004655:Emulsions / Q000008:administration & dosage; D005227:Fatty Acids / Q000378:metabolism; D005395:Fish Oils / Q000008:administration & dosage*; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019308:Palmitic Acid / Q000008:administration & dosage / Q000378:metabolism; D010288:Parenteral Nutrition; D010743:Phospholipids / Q000008:administration & dosage*; D013024:Soybean Oil / Q000008:administration & dosage*; D013552:Swine / Q000254:growth & development / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D004042:Dietary Fats, Unsaturated; D004655:Emulsions; D005227:Fatty Acids; D005395:Fish Oils; D010743:Phospholipids; D014280:Triglycerides; C568345:fish oil triglycerides; C545823:soybean oil, phospholipid emulsion; D019308:Palmitic Acid; D013024:Soybean Oil
keywords: fish oil; lipidomics; medium-chain triglycerides; metabolomics; parenteral nutrition-associated liver disease; soybean oil; total parenteral nutrition; transcriptomics; vitamin E