TY - JOUR
T1 - Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions
AU - Guthrie, Gregory
AU - Kulkarni, Madhulika
AU - Vlaardingerbroek, Hester
AU - Stoll, Barbara
AU - Ng, Kenneth
AU - Martin, Camilia
AU - Belmont, John
AU - Hadsell, Darryl
AU - Heird, William
AU - Newgard, Christopher B.
AU - Olutoye, Oluyinka
AU - Van Goudoever, Johannes
AU - Lauridsen, Charlotte
AU - He, Xingxuan
AU - Schuchman, Edward H.
AU - Burrin, And Douglas
N1 - Funding Information:
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
PY - 2016/9
Y1 - 2016/9
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 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.
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 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.
KW - Fish oil
KW - Lipidomics
KW - Medium-chain triglycerides
KW - Metabolomics
KW - Parenteral nutrition-associated liver disease
KW - Soybean oil
KW - Total parenteral nutrition
KW - Transcriptomics
KW - Vitamin E
UR - http://www.scopus.com/inward/record.url?scp=84989266781&partnerID=8YFLogxK
U2 - 10.1194/jlr.M069526
DO - 10.1194/jlr.M069526
M3 - Article
C2 - 27474222
AN - SCOPUS:84989266781
SN - 0022-2275
VL - 57
SP - 1696
EP - 1711
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 9
ER -