Biliary excretion of apolipoprotein B by the isolated perfused rat liver. Relationship to receptor-mediated uptake of human low-density lipoprotein and biliary lipid secretion

[[abstract]]Since we previously reported that apolipoproteins, the lipid transport proteins of lipoproteins, are present in human bile, we tested the hypothesis that apolipoproteins in bile are derived from circulating lipoproteins and that they are involved in the biliary excretion of lipids. We perfused isolated rat livers with lipoprotein-free solutions and collected bile before and after addition of human low and high density lipoproteins. When human low density lipoprotein was added to solutions perfusing livers isolated from rats previously treated with ethinyl estradiol, a hormone that increases receptor-mediated uptake of low density lipoproteins by hepatocytes, the concentrations in bile of cholesterol and phospholipid, but not bile acids, increased by approximately 25% together with the appearance of small amounts (approximately 1% of the amount perfused) of a metabolized form of human apolipoprotein B in bile. Acetylation of low density lipoprotein, a procedure that prevents this lipoprotein from binding to its receptor on hepatocytes, both abolished the appearance of immunoreactive apolipoprotein B in bile and blocked the increase in biliary cholesterol and phospholipid concentrations. Whereas the addition of a high density lipoprotein to solutions perfusing isolated livers of normal rats was associated with the appearance of small amounts (approximately 1% of the amount perfused) of apolipoproteins A-I and A-II in bile, there were no accompanying changes in the concentrations of biliary lipids. These results suggest that apolipoproteins or their fragments in bile are derived from circulating lipoproteins; in the case of apolipoprotein B, biliary excretion is dependent upon receptor-mediated uptake of low density lipoprotein by the hepatocyte. Our data are also consistent with the hypothesis that certain apolipoproteins may be involved in biliary lipid secretion, although in an as yet unclear manner