The effects of xenobiotics on hepatic lipid and lipo-protein metabolism.

The liver occupies a central position in lipid and lipo-protein metabolism. Its function includes lipid and lipoprotein biosynthesis, assembly, packaging, transport, secretion, uptake and degradation of lipoproteins. In addition, enzymes synthesized and secreted by the liver into the blood stream or remaining bound to the endothelial cells in the capillaries, affect lipoprotein metabolism in the circulation. Xenobiotics may influence each of these steps. The mechanisms include more specific actions such as hormone or transmitter agonism and antagonism, membrane effects (stabilization or changes in trans-membrane gradients), influence on protein synthesis, influence on lipid metabolism by induction or inhibition of involved enzymes, or more general actions such as disturbances or damage of cellular membranes and cellular function. Some of these effects can easily be described as pharmacological actions, more or less independent of specific requirements in the chemical structure of the xenobiotics. Others are linked to specific chemical substituents such as carboxyl or alcoholic hydroxyl groups allowing the formation of lipid-xenobiotic-conjugates and/or the channeling of xenobiotics into lipid metabolism. This review will give a short overview of the mechanisms of xenobiotic-influenced hepatic lipid and lipoprotein metabolism.