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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD027448-02
Application #
3426679
Study Section
Special Emphasis Panel (SRC (R0))
Project Start
1990-09-01
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045