Cysteine Supplementation and Reduction of Total Parenteral Nutrition—Induced Hepatic Lipid Accumulation in the Weanling Rat

Abstract

SummaryTotal 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.