Post-translational events in the intracellular transit of apolipoprotein-B: modulation by dietary lipids.

Triacylglycerol and cholesteryl esters are transported in the blood as components of the plasma lipoproteins. Endogenous triacylglycerol synthesized by the liver is secreted into the plasma in the form of VLDL, which consists of a droplet of non-polar lipid (predominantly triacylglycerol with a variable amount of cholesteryl ester), stabilized by an outer shell of phospholipid, cholesterol and protein. Apolipoprotein-B (apo-B) is the major protein of VLDL. Although apo-B is an essential component of VLDL, secretion is driven by provision of substrates to the liver for triacylglycerol synthesis. These include glucose and nonesterified fatty acids. The composition and size of VLDL is influenced by the substrate provided (Sniderman & Cianflone, 1993). Dietary experiments and experiments using isolated hepatocytes have shown that provision of carbohydrates increases synthesis of triacylglycerol-enriched, larger, lighter VLDL (VLDLl), while provision of fatty acids results in production of smaller, denser VLDL (VLDL2). Since VLDLl are cleared rapidly from the circulation, while VLDL2 are cleared more slowly and are converted to the atherogenic LDL, the nature of VLDL secreted by the liver is an important determinant of cardiovascular risk (Packard et al. 1984; Shepherd & Packard, 1987). An understanding of the mechanisms involved in regulation of the assembly of VLDL and the factors determining their composition is, therefore, extremely important.