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 heal bile acid transport on the regulation of classic and alternative bile acid synthesis in cholesterol-fed rats and ra bbits. Bile acid pool sizes, fecal bile acid outputs (synthesis rates), and the activities of cholesterol 7 alpha-hydroxylase (classic bile acid synth esis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to heal bile acid transporter expression (ileal apical sodium-depe ndent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.1-time s in rats (98 +/- 19 mg/dl) and 31-times (986 +/- 188 mg/dl) in rabbits. Th e bile acid pool size remained constant (55 +/- 17 mg vs. 61 +/- 18 mg) in rats but doubled (254 +/- 46 to 533 +/- 53 mg) in rabbits. ASBT protein exp ression did not change in rats but rose 31% (P < 0.05) in rabbits, Fecal bi le acid outputs that reflected bile acid synthesis increased 2- and 2.4-tim es (P < 0.05) in cholesterol-fed rats and rabbits, respectively. Cholestero l 7 alpha-hydroxylase activity rose 33% (24 +/- 2.4 vs. 18 +/- 1.6 pmol/mg/ min, P < 0.01) and mRNA levels increased 50% (P < 0.01) in rats but decreas ed 68% and 79%, respectively, in cholesterol-fed rabbits. Cholesterol 27-hy droxylase activity remained unchanged in rats but rose 62% (P < 0.05) in ra bbits. Classic bile acid synthesis (cholesterol 7 alpha-hydroxylase) was in hibited in rabbits because an enlarged bile acid pool developed from enhanc ed ileal bile acid transport. In contrast, in rats, cholesterol 7 alpha-hyd roxylase was stimulated but the bile acid pool did not enlarge because ASBT did not change. jlr Therefore, although bile acid synthesis was increased via different pathways in rats and rabbits, enhanced ileal bile acid transp ort was critical for enlarging the bile acid pool size that exerted feedbac k regulation on cholesterol 7 alpha-hydroxylase in rabbits.