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. Tritiated glycerol incorporation into media lipids secreted by hepatocytes isolated from TPN-treated animals was 45% of that from cysteine-supplemented animals, suggesting a defect in hepatic lipid secretion associated with TPN-induced hepatic steatosis in the weanling rat that is partially corrected by cysteine supplementation.