Studies in three major areas within the broad field of intestinal and hepatic lipid metabolism and physiology are described, which are designed to pursue promising new extensions of on-going work in this laboratory. 1. Studies of cytoplasmic fatty acid binding protein (FABP). The originally proposed transport function of this protein will be more directly investigated and broader aspects of its relationship to cellular fatty acid economy will be explored, including effects on synthesis, esterification and oxidation. Experimental findings will be related to the pathophysiology of fatty acid metabolism and transport. 2. Studies of bile secretion. The effect of bile acids, dietary lipids and pharmacological agents on lipid composition and fluidity of the canalicular membrane, and its relationship to bile secretory processes including the activity of NaK-ATPase, bile acid and lipid secretion, and bile acid """"""""independent"""""""" water flow will be examined. Morphometric studies of hepatocyte ultrastructure will be extended with particular reference to the Golgi apparatus and its possible relation to bile secretion. 3. Interrelationship between bile acid and triglyceride metabolism. The apparent relationship between bile acid and triglyceride metabolism as suggested by several lines of clinical evidence, will be elucidated. Experimental approaches will include studies of the laboratory rat, the isolated perfused liver and isolated hepatocytes, as well as the effect of controlled interruption of the enterohepatic circulation on plasma VLDL triglycerides in man and Rhesus monkey. These experiments are expected to provide important new information concerning the physiology and pathophysiology of the digestive system, and its relationship to clinical disorders of lipid transport and metabolism.
