Accumulating evidence indicates that certain nutritionally essential microelements (trace elements), including zinc and copper, may play an important role in cholesterol metabolism and perhaps ultimately in atherosclerotic process. The underlying mechanisms of their action on cholesterol metabolism have, however, been meagerly documented. The studies are designed to investigate 1) the intestinal absorption of cholesterol involving chylomicrons and the compositional and morphological characteristics of chylomicrons as affected by the nutritional status of copper, 2) the peripheral lipolysis of chylomicrons subsequent to their entry into the circulation, and 3) the hepatic uptake and plasma clearance of chylomicron remnants, as influenced by zinc and copper status. This work will be conducted using adult male rats fed semi-purified diets. The diets will be formulated to produce a marginal level of zinc (or copper) deficiency in order to avoid a drastic reduction in food intake and weight gain and to better simulate the suboptimal levels of zinc and copper intake, which have been known to exist in human population. The intestinal absorption of dietary cholesterol will be determined by cannulating the intestinal lymph duct. The procedure consists of the administration of 14C-cholesterol in a lipid emulsion into the small intestine and measurement of 14C-radioactivity appearing in the lymphatic fluid. Chylomicrons formed during the transport of lipids will be obtained by the method of lymph duct cannulation. Studies on subsequent isolation and characterization of chylomicrons will include the use of ultra-centrifugation, chromatography, electron microscopy and gel electrophoretic techniques. The measurement of the rate of peripheral lipolysis of chylomicrons will involve the administration of lymph chylomicron doubly labeled with 3H-retinyl ester and 14C-triglyceride into functionally hepatectomized evicerated rats and measurement of the changes in the ratio of 14C/3H at specific time intervals. Investigation of the rate of plasma clearance and hepatic uptake of chylomicron remnants will be performed by time-course measurements of 3H and 14C-radioactivities in the plasma and liver after administration of chylomicron remnants labeled with 3H-retinyl ester and 14C-cholesterol as the marker.
NIH ExPorter
NIH ExPorter