Total parenteral nutrition (TPN) is a vital feeding technique for individuals who are unable to tolerate oral nutrition. Hepatic dysfunction characterized by hepatic steatosis is a serious and frequent complication of TPN; the glucose-lipid composition of TPN affects the development of hepatic steatosis. The somatomedins, insulin-like growth factors I and II (IGF-I and -II) are polypeptide, mitogenic hormones primarily secreted by the liver. They are regulated by growth hormone,insulin and nutritional status; hepatic dysfunction may also affect their synthesis. The long-term objective of this research is to understand the mechanisms by which the nutrient composition of TPN,hepatic function and somatomedin responses interact in order to devise TPN formulations/protocols which will minimize hepatic dysfunction and improve anabolism. The specific research aims are: 1. to determine in rats nourished by TPN the effects of varying amounts of glucose and lipid from either medium chain triglyceride (MCT) or long chain triglyceride (LCT) fat emulsions on: hepatic lipid content,insulin sensitivity, serum somatomedin levels and growth. TPN feeding studies will be conducted using 40%, 60% or 80% of nonprotein calories from LCT or 75% MCT/25% LCT fat emulsions in 2- and 3-way factorial designs. 2. to determine the relationship between TPN-induced hepatic dysfunction and serum levels of the somatomedins and their binding protein. Hepatic steatosis will be induced by TPN and serum somatomedin in levels will then be measured using an """"""""IGF Challenge Test"""""""". 3. to determine the mechanisms by which somatomedin levels and/or growth are altered with TPN. First, to test different TPN formulations alter hepatic somatomedin synthesis by determining the steady abundance of hepatic IGF-I mRNA. Second, to test if differences in insulin sensitivity with high-fat TPN alter the binding of IGF-I to peripheral receptors by using membrane preparations from selected tissues obtained from rats with insulin resistance or altered IGF-I levels. 4. to determine if confusion of IGF-I with different TPN formulations will improve the anabolic response to TPN in a rat surgical stress model. Anabolic response will be assessed by growth, N balance, and rates of protein synthesis in liver and skeletal muscle.
