New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs.
Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fish oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fish oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14 day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7α-hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OSTα) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both OV and SL emulsions. Due to the presence of phytosterols in the SL emulsion, the differences in cholestasis and liver injury among lipid emulsion groups in vivo were weakly correlated with plasma and hepatic phytosterol content.
Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
Hester
H
Vlaardingerbroek
Kenneth
K
Ng
Barbara
B
Stoll
Nancy
N
Benight
Shaji
S
Chacko
Leo A J
LA
Kluijtmans
Wim
W
Kulik
E James
EJ
Squires
Oluyinka
O
Olutoye
Deborah
D
Schady
Milton L
ML
Finegold
Johannes B
JB
van Goudoever
Douglas G
DG
Burrin
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002478:Cells, Cultured; D002783:Cholestenones / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D008107:Liver Diseases / Q000209:etiology / Q000517:prevention & control*; D000069463:Olive Oil; D010288:Parenteral Nutrition / Q000009:adverse effects / Q000379:methods*; D010938:Plant Oils / Q000008:administration & dosage; D011247:Pregnancy; D047928:Premature Birth / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013024:Soybean Oil / Q000008:administration & dosage; D013552:Swine; D013553:Swine Diseases / Q000209:etiology / Q000517:prevention & control*; D014280:Triglycerides / Q000008:administration & dosage; D005723:gamma-Glutamyltransferase / Q000097:blood
D002783:Cholestenones; D005217:Fat Emulsions, Intravenous; D005395:Fish Oils; D008055:Lipids; D000069463:Olive Oil; D010938:Plant Oils; D014280:Triglycerides; C002656:7 alpha-hydroxy-4-cholesten-3-one; D013024:Soybean Oil; D002790:Cholesterol 7-alpha-Hydroxylase; D005723:gamma-Glutamyltransferase
FGF19; cholestasis; fish oil; parenteral nutrition-associated liver disease; soybean oil