Total parenteral nutrition (TPN) induced hepatic steatosis is a common complication in man. Although unproven, it may be the first hepatic lesion in the progression to TPN-induced liver disease. We propose to study the contribution of alterations in hepatic lipogenesis and alterations in lipoprotein assembly and secretion to the development of TPN-induced steatosis in the weanling rat. Thirty-day-old weanling rats will receive TPN, 0.9% NaCl with pair feeding for comparable weight gain, or rat chow for 7 days. In this model, the TPN treated animals consistently develop hepatic steatosis. Lipogenesis will be determined by 3H20 incorporation into lipid in hepatocytes isolated from all groups. The activity and mRNA levels for acetyl-CoA-carboxylase (ACC), the rate limiting enzyme in lipogenesis, will be determined in the livers of all groups, and correlated with lipogenic rates. Apolipoprotein B (Apo B) will be quantitated by immunoprecipitation and mRNA-Apo B by northern and slot blot. The secretion rates for albumin and Apo B will be determined in primary culture of hepatocytes from TPN and control rats by 35S-methionine labelling and pulse chase experiments. The lipogenic rates and ACC levels will be compared to total hepatic lipid, histologic grading, and serum insulin and glucagon levels. Similarly, Apo B levels and secretion will be compared to hepatic lipid and histology. By defining the role of lipogenesis and lipid transport in the hepatic steatosis TPN, appropriate hormonal or nutritional therapy may be designed to prevent this complication.
| Narkewicz, M R; Caldwell, S; Jones, G (1995) Cysteine supplementation and reduction of total parenteral nutrition-induced hepatic lipid accumulation in the weanling rat. J Pediatr Gastroenterol Nutr 21:18-24 |
