Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits.

We investigated the effect of ileal bile acid trans- port on the regulation of classic and alternative bile acid synthesis in cholesterol-fed rats and rabbits. Bile acid pool sizes, fecal bile acid outputs (synthesis rates), and the activi- ties of cholesterol 7 a -hydroxylase (classic bile acid synthe- sis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to ileal bile acid transporter expres- sion (ileal apical sodium-dependent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.1-times in rats (98 6 19 mg/dl) and 31-times (986 6 188 mg/dl) in rabbits. The bile acid pool size remained constant (55 6 17 mg vs. 61 6 18 mg) in rats but doubled (254 6 46 to 533 6 53 mg) in rabbits. ASBT protein expression did not change in rats but rose 31% ( P , 0.05) in rabbits. Fecal bile acid outputs that reflected bile acid synthesis increased 2- and 2.4-times ( P , 0.05) in cholesterol-fed rats and rabbits, respectively. Cho- lesterol 7 a -hydroxylase activity rose 33% (24 6 2.4 vs. 18 6 1.6 pmol/mg/min, P , 0.01) and mRNA levels increased 50% ( P , 0.01) in rats but decreased 68% and 79%, respec- tively, in cholesterol-fed rabbits. Cholesterol 27-hydroxylase activity remained unchanged in rats but rose 62% ( P , 0.05) in rabbits. Classic bile acid synthesis (cholesterol 7 a - hydroxylase) was inhibited in rabbits because an enlarged bile acid pool developed from enhanced ileal bile acid