TY - JOUR
T1 - Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions
AU - Guthrie, G.
AU - Kulkarni, M.
AU - Vlaardingerbroek, H.
AU - Stoll, B.
AU - Ng, K.
AU - Martin, C.
AU - Belmont, J.W.
AU - Hadsell, D.
AU - Heird, W.
AU - Newgard, C. B.
AU - Olutoye, O.
AU - van Goudoever, J.
AU - Lauridsen, C.
AU - He, X. X.
AU - Schuchman, E. H.
AU - Burrin, D.
N1 - M1 - 9
ISI Document Delivery No.: DW1VR Times Cited: 0 Cited Reference Count: 61 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 U.S. Department of Agriculture [58-6250-6-001]; American Society for Parenteral and Enteral Nutrition; Texas Medical Center Digestive Diseases Center (National Institutes of Health) [P30 DK56338]; Foundation for the National Institutes of Health [DK094616]; National Institutes of Health [T32-DK07664]; Whitlock Foundation; Ter Meulen Fund of the Royal Netherlands Academy of Arts and Sciences; Young Investigator Exchange Program of the International Pediatric Research Foundation; Sophia Kinderziekenhuis Fonds, Rotterdam, The Netherlands This work was supported in part by federal funds from the U.S. Department of Agriculture under Cooperative Agreement Number 58-6250-6-001, the American Society for Parenteral and Enteral Nutrition, the Texas Medical Center Digestive Diseases Center (National Institutes of Health Grant P30 DK56338), and Foundation for the National Institutes of Health Grant DK094616 (D.B.). Additional support was provided by National Institutes of Health Grant T32-DK07664 (G.G.), funds from the Whitlock Foundation (M.K.), the Ter Meulen Fund of the Royal Netherlands Academy of Arts and Sciences (H.V.), a grant from the Young Investigator Exchange Program of the International Pediatric Research Foundation (H.V.), and a research fellowship grant of the Sophia Kinderziekenhuis Fonds, Rotterdam, The Netherlands (H.V.). D.B. received lipid emulsions donated from Fresenius Kabi for the study. All other authors declare no financial conflicts of interest. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 0 4 AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC BETHESDA J LIPID RES
PY - 2016
Y1 - 2016
N2 - 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 C-13-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.
AB - 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 C-13-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.
U2 - 10.1194/jlr.M069526
DO - 10.1194/jlr.M069526
M3 - Article
C2 - 27474222
VL - 57
SP - 1696
EP - 1711
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
ER -