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 transport 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 activities of cholesterol 7alpha-hydroxylase (classic bile acid synthesis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to ileal bile acid transporter expression (ileal apical sodium-dependent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.1-times in rats (98 +/- 19 mg/dl) and 31-times (986 +/- 188 mg/dl) in rabbits. The 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 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. Cholesterol 7alpha-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 decreased 68% and 79%, respectively, 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 7alpha-hydroxylase) was inhibited in rabbits because an enlarged bile acid pool developed from enhanced ileal bile acid transport. In contrast, in rats, cholesterol 7alpha-hydroxylase was stimulated but the bile acid pool did not enlarge because ASBT did not change. Therefore, although bile acid synthesis was increased via different pathways in rats and rabbits, enhanced ileal bile acid transport was critical for enlarging the bile acid pool size that exerted feedback regulation on cholesterol 7alpha-hydroxylase in rabbits.

[1]  F. Suchy,et al.  Sorting of rat liver and ileal sodium-dependent bile acid transporters in polarized epithelial cells. , 1998, American journal of physiology. Gastrointestinal and liver physiology.

[2]  M. Trauner,et al.  Neither intestinal sequestration of bile acids nor common bile duct ligation modulate the expression and function of the rat ileal bile acid transporter , 1998, Hepatology.

[3]  S. Grundy,et al.  Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations. , 1998, The Journal of clinical investigation.

[4]  D. Greenblatt,et al.  Increased bile acid pool inhibits cholesterol 7 alpha-hydroxylase in cholesterol-fed rabbits. , 1997, Gastroenterology.

[5]  P. Dawson,et al.  Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid. , 1997, Gastroenterology.

[6]  K. Setchell,et al.  Fetal and Neonatal Expression of the Apical Sodium-Dependent Bile Acid Transporter in the Rat Ileum and Kidney1 , 1997, Pediatric Research.

[7]  G. Ness,et al.  Increasing hepatic cholesterol 7α‐hydroxylase reduces plasma cholesterol concentrations in normocholesterolemic and hypercholesterolemic rabbits , 1996, Hepatology.

[8]  L. Agellon,et al.  Coordinate regulation of bile acid biosynthetic and recovery pathways. , 1996, Biochemical and biophysical research communications.

[9]  C. Steer,et al.  Regulation of bile acid synthesis by deoxycholic acid in the rat: Different effects on cholesterol 7α‐hydroxylase and sterol 27‐hydroxylase , 1995, Hepatology.

[10]  G. Ness,et al.  Treatment of the cholesterol biosynthetic defect in Smith-Lemli-Opitz syndrome reproduced in rats by BM 15.766. , 1995, Gastroenterology.

[11]  C. Steer,et al.  Regulation of bile acid synthesis by deoxycholic acid in the rat: Different effects on cholesterol 7α-hydroxylase and sterol 27-hydroxylase , 1995 .

[12]  T. Parker,et al.  Unexpected inhibition of cholesterol 7 alpha-hydroxylase by cholesterol in New Zealand white and Watanabe heritable hyperlipidemic rabbits. , 1995, The Journal of clinical investigation.

[13]  J. Horton,et al.  Regulation of Hepatic 7α-Hydroxylase Expression and Response to Dietary Cholesterol in the Rat and Hamster (*) , 1995, The Journal of Biological Chemistry.

[14]  P. Dawson,et al.  Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter. , 1995, The Journal of clinical investigation.

[15]  J. Gordon,et al.  The mouse ileal lipid-binding protein gene: a model for studying axial patterning during gut morphogenesis , 1994, The Journal of cell biology.

[16]  M. Wilson,et al.  Dietary cholesterol and downregulation of cholesterol 7 alpha-hydroxylase and cholesterol absorption in African green monkeys. , 1994, The Journal of clinical investigation.

[17]  L. Johnson,et al.  Physiology of the gastrointestinal tract , 2012 .

[18]  S. Smith,et al.  Bile acid excretion and cholesterol 7 alpha-hydroxylase expression in hypercholesterolemia-resistant rabbits. , 1993, Journal of lipid research.

[19]  G. Wess,et al.  Intestinal bile acid absorption. Na(+)-dependent bile acid transport activity in rabbit small intestine correlates with the coexpression of an integral 93-kDa and a peripheral 14-kDa bile acid-binding membrane protein along the duodenum-ileum axis. , 1993, The Journal of biological chemistry.

[20]  H. Fasold,et al.  Characterization and chemical modification of the Na(+)-dependent bile-acid transport system in brush-border membrane vesicles from rabbit ileum. , 1992, Biochimica et biophysica acta.

[21]  G. Ness,et al.  Differing effects of cholesterol and taurocholate on steady state hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities and mRNA levels in the rat. , 1992, Journal of lipid research.

[22]  G. Ness,et al.  Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit. , 1992, Gastroenterology.

[23]  J. Cuthbert,et al.  Regulation of hepatic sterol metabolism in the rat. Parallel regulation of activity and mRNA for 7 alpha-hydroxylase but not 3-hydroxy-3-methylglutaryl-coenzyme A reductase or low density lipoprotein receptor. , 1992, The Journal of biological chemistry.

[24]  I. Björkhem,et al.  On the mechanism of stimulation of cholesterol 7α-hydroxylase by dietary cholesterol , 1991 .

[25]  G. Ness,et al.  Feedback regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity by dietary cholesterol is not due to altered mRNA levels. , 1991, The Journal of biological chemistry.

[26]  P. Hylemon,et al.  Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by taurocholate and cholesterol in the chronic biliary diverted rat. , 1991, The Journal of biological chemistry.

[27]  C. Slaughter,et al.  Cloning and regulation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis. , 1990, The Journal of biological chemistry.

[28]  M. Poznansky,et al.  Cholesterol-mediated regulation of HMG-CoA reductase in microsomes from human skin fibroblasts and rat liver. , 1990, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[29]  D. Hewett‐Emmett,et al.  Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits. , 1989, Journal of lipid research.

[30]  D. McNamara,et al.  The effect of abnormal plasma and cellular sterol content and composition on low density lipoprotein uptake and degradation by monocytes and lymphocytes in sitosterolemia with xanthomatosis. , 1988, Metabolism: clinical and experimental.

[31]  T. Parker,et al.  Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity. , 1987, The Journal of clinical investigation.

[32]  M. Katan,et al.  Characteristics of human hypo- and hyperresponders to dietary cholesterol. , 1987, American journal of epidemiology.

[33]  P. Demacker,et al.  Partial ileal bypass reduces the production rate of low density lipoproteins in Watanabe heritable hyperlipidemic rabbits. , 1984, Journal of lipid research.

[34]  M. Brown,et al.  Saturation and suppression of hepatic lipoprotein receptors: a mechanism for the hypercholesterolemia of cholesterol-fed rabbits. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[35]  P. Klein,et al.  An improved procedure for the synthesis of glycine and taurine conjugates of bile acids. , 1977, Journal of lipid research.

[36]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[37]  R. Dowling,et al.  The control of bile acid pool size: Effect of jejunal resection and phenobarbitone on bile acid metabolism in the rat 1 , 1974, Gut.

[38]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[39]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[40]  Guorong Xu,et al.  Increasing dietary cholesterol induces different regulation of classic and alternative bile acid synthesis. , 1999, The Journal of clinical investigation.

[41]  A. Hofmann.  Intestinal absorption of bile acids and biliary constituents , 1994 .

[42]  A. Hofmann,et al.  Negative feedback regulation of the ileal bile acid transport system in rodents. , 1993, Gastroenterology.

[43]  Heterogeneity of cholesterol homeostasis in humans. , 1987, Nutrition reviews.