Regulation and interaction of cholesterol, bile salt and lipoprotein synthesis in liver

The liver is the junction of several inter-organ metabolic cycles which are essential for the homeostasis of mammalian metabolism. Two of these are described in greater detail and their role in control of lipid metabolism will be presented. The fatty acid-triglyceride cycle is of particular importance for our understanding of the mechanisms governing serum lipid levels. This is due to the fact that the lipoprotein secreted by the liver in the course of this metabolic cycle - very low density lipoprotein - has a relatively long half-life in the plasma compartment. Data have been collected from the literature to show that different nutritional and pharmacological stimuli affecting serum lipid levels do so by interfering with the rate of very low density lipoprotein input into the plasma compartment. The enterohepatic circulation of steroids is another cycle which contributes to control of lipid metabolism. Data are presented which show that bile acids, the major steroids circulating in this cycle, exert direct feedback control of hepatic cholesterol synthesis. This characteristic of bile acids may explain why certain bile acids, when given orally, reduce serum cholesterol levels. Several clinical and experimental observations suggest a close relation between bile acid and triglyceride metabolism. It is characterized by an inverse relation between bile acid pool size and serum triglyceride levels. Moreover, a reduction of the bile acid pool size is accompanied by an enhanced hepatic fatty acid and triglyceride synthesis and secretion into blood. The molecular basis and physiological significance of these observations have still to be explored.(ABSTRACT TRUNCATED AT 250 WORDS)