Induction of bile acid synthesis by cholesterol and cholestyramine feedingis unimpaired in mice deficient in apolipoprotein AI

High density lipoprotein (HDL) cholesterol is believed to be preferentially utilized for bile acid synthesis and biliary secretion. In mice, the delet ion of apolipoprotein AI (apo AI), the major apolipoprotein in HDL, results in very low plasma HDL-cholesterol levels. This article describes bile aci d metabolism in apo AI-deficient (Apo AI(-/-)) mice and their C57BL/6 (Apo AI(+/+)) controls fed either a basal rodent diet alone or containing choles terol or cholestyramine. Basal plasma HDL-cholesterol levels in the (-/-) m ice (<10 mg/dL) were less than 20% of those in their (+/+) controls, but th ere were no phenotypic differences in either the relative cholesterol conte nt of gallbladder bile, bile acid pool size and composition, fecal-bile aci d excretion or the activity of, or mRNA level for, cholesterol 7<alpha>-hyd roxylase. However, compared with their (+/+) controls, the (-/-) mice absor bed more cholesterol (33 vs. 24%) and manifested lower rates of hepatic ste rol synthesis (534 vs. 1,019 nmol/h per g). Cholesterol feeding increased h epatic cholesterol levels in the (+/+) animals from 2.7 to 4.4 mg/g and in the (-/-) mice from 2.6 to 8.1 mg/g. Bile acid synthesis increased 70% in b oth genotypes. Cholestyramine feeding stimulated bile acid synthesis 3.7 fo ld in both (-/-) and (+/+) mice. We conclude that the virtual loss of HDL-c holesterol from the circulation in apo AI deficiency has no impact on the a bility of the hepatocyte to adapt its rate of bile acid synthesis in concer t with the amount of cholesterol and bile acid returning to the liver from the small intestine.