THE REGULATION OF INTESTINAL LIPID TRANSPORT

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The major thrust of this project is to understand the factors that control the delivery of dietary lipids into the lymph. Lipids that are not transported in the lymph enter a storage pool and subsequently the circulation via the portal vein. These portal lipids are likely to be taken up by the liver rather than by more peripheral tissues as occurs with the lipids transported in lymph. The liver in part secretes these dietary lipids as VLDL. The end result of VLDL catabolism is LDL, the major cholesterol carrier in the plasma. The current proposal first seeks to determine the size of the mucosal neutral lipid storage pool on intraduodenal glyceryltrioleate infusion as influenced by physiological manipulations such as bile duct cannulation which is expected to increase its size and phosphatidylcholine co-infusion which is likely to decrease it. The pool is isolated, its size determined and characterized as to its acyl group composition using BPLC and GLC methodology. Since the storage pool contains considerable endogenous acyl groups, the second and third aim is to determine the origin of these groups. Using intravenous infusions of fatty acid (second aim) or chylomicron and VLDL remnants (third aim), the mucosa will be assayed for uptake of these lipids and the potential of regulating uptake under differing physiological conditions where the storage pool is expected to expand or contract. The fourth aim is to characterize the acyl group composition of the triacylglycerols in chylomicrons, VLDL, mucosa, storage pool, microsomes and Golgi under differing physiological conditions. The acyl groups will be determined by HPLC and GLC methodology. The object is to compare the acyl constituents in each compartment to try to understand where the triacylglycerol stream splits between that going into lymph as represented by chylomicrons and VLDL and that going into the storage pool. This may be revealed as differences in triacylglycerol composition between microsomes and Golgi with the Golgi having acyl groups similar to dietary lipids and the microsomes having an acyl group composition composed of more exogenous lipids. The fifth aim examines membrane movement from microsomes to Golgi under varying levels of lymphatic triacylglycerol transport. Vesicular traffic efficiency between these two organelles may play a role in the ability of the intestine to transport lipid. Pulse-chase kinetics will be used. The budding of vesicles from microsomes requires protein acylation and the ability of the intestine to do this will be studied under conditions of differing lymphatic triacylglycerol transport. The origin of the acyl group from triacylglycerol or phosphatidylcholine will be investigated as will the acyl group of choice, palmitate or oleate.