Cysteine supplementation and reduction of total parenteral nutrition-induced hepatic lipid accumulation in the weanling rat.
Total parenteral nutrition (TPN)-induced hepatic steatosis is the most common complication of TPN administration to humans. The mechanism of TPN-induced hepatic steatosis has not been studied in young mammals. The goal of this study was to determine the mechanism of TPN-induced hepatic steatosis in the weanling rat and the effect of supplementation of TPN with choline and/or cysteine on TPN-induced hepatic steatosis. In the weanling rat, we investigated the effect of TPN administration on histologic hepatic steatosis, total hepatic lipid, hepatic acetyl-CoA-carboxylase (ACC--the rate limiting enzyme in fatty acid synthesis) specific activity, and total plasma lipids. TPN administration resulted in a threefold increase in hepatic lipid as compared with control and sham animals (TPN 138 +/- 12 mg/g liver versus control 57 +/- 1), an increase in histologic steatosis (TPN 3.7 versus control 1.3), and a decline in total plasma lipid (TPN 2.1 +/- 0.3 g/L versus control 4.1 +/- 0.3). TPN-induced hepatic steatosis in the weanling rat was not associated with an increase in ACC specific activity (TPN 2.10 +/- 0.33 nmol/min/mg protein versus control 2.85 +/- 0.23). Supplementation of the TPN with choline (15 mg/day) did not significantly lessen hepatic steatosis; however, supplementation of TPN with cysteine (2.5 mg/day) or with cysteine and choline did result in a significant lessening of hepatic lipid content and of histologic steatosis and a normalization of total plasma lipid.(ABSTRACT TRUNCATED AT 250 WORDS)
Narkewicz
M R
MR
Department of Pediatrics, University of Colorado School of Medicine, Denver, USA.
Caldwell
S
S
Jones
G
G
D000103:Acetyl-CoA Carboxylase / Q000032:analysis; D000818:Animals; D000833:Animals, Suckling / Q000254:growth & development; D002478:Cells, Cultured; D002794:Choline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003545:Cysteine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005234:Fatty Liver / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D005527:Food, Fortified; D005990:Glycerol / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010289:Parenteral Nutrition, Total / Q000009:adverse effects / Q000592:standards*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014886:Weaning
D008055:Lipids; D000103:Acetyl-CoA Carboxylase; D003545:Cysteine; D002794:Choline; D005990:Glycerol