Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit

Xu, Guowang; Salen, Gerald; Batta, Ashok K.; Shefer, Sarah; Nguyen, Lien; Niemann, Wendell H.; Chen, Thomas S.; Arora-Mirchandani, R.; Ness, Gene C.; Tint, G. Stephen

doi:10.1016/0016-5085(92)91735-m

Cited by 23 publications

(8 citation statements)

References 16 publications

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“…44,45 Inhibition of biliary de novo cholesterol secretion was observed only for supraphysiological doses of cholate, most likely by inhibiting cholesterol synthesis late during the experiment. This is in line with data obtained in rabbits, 59 but not in rats, 42 indicating a species difference. However, increased availability of preformed cholesterol during high-dose cholate infusion either from intestinal 60,61 and/or hepatic 58 sources may have contributed to the lower proportion of de novo cholesterol.…”

Section: Discussionsupporting

confidence: 92%

Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol

et al. 1999

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Hepatic bile acid synthesis is regulated by recirculating bile acids, possibly by modulating the availability of newly synthesized and preformed cholesterol. Because data in the hamster on this mechanism are lacking, we fitted these animals with an extracorporeal bile duct and administered tritiated water intraperitoneally to label newly formed cholesterol. After interruption of the enterohepatic circulation, physiological and double-physiological doses of conjugated cholate (25 or 50 mol/100 g · h) or of unconjugated deoxycholate (6 or 12 mol) were infused intraduodenally for 54 hours and compared with controls. De novo and preformed cholesterol directly secreted into bile or used for cholate and chenodeoxycholate synthesis were quantitated by high-pressure liquid chromatography (HPLC)-liquid scintillation. Directly after depletion of the bile acid pool (6-9 hours) at nearly physiological conditions, chenodeoxycholate synthesis was significantly reduced by cholate and deoxycholate by up to 45% to 51%, whereas cholate formation decreased by Ϸ22% during deoxycholate. This short-term effect was mainly mediated by reduced synthesis from preformed cholesterol. After long-term bile depletion (30-54 hours), bile acid synthesis returned to control levels during 25 mol of cholate and of both deoxycholate doses. In contrast, only 50 mol of cholate prevented derepression of bile acid synthesis. This long-term effect was mainly attributed to a diminished formation from de novo cholesterol exceeding the reduced synthesis from preformed cholesterol. In summary, short-and long-term regulation of bile acid synthesis in hamsters differs with respect to availabilities of preformed and de novo cholesterol. (HEPATOL-OGY 1999;30:230-237.)

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Section: Discussionsupporting

confidence: 92%

Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol

et al. 1999

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“…In addition, bile fistulas were constructed in 5 cholesterol-fed and 4 control rats, and 5 cholesterol-fed and 5 control rabbits after the feeding. The surgical procedure established a bile fistula for the recovery of bile acids in rats and was similar to that for rabbits as described previously (24). Bile was collected continuously for 2 days in rats and 5 days in rabbits as the bile acid pool is completely depleted in 24 h in rats and in 3 days in rabbits.…”

Section: Animal Experimentsmentioning

confidence: 99%

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

Bl²,

Shefer

et al. 2000

Journal of Lipid Research

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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 7 ␣ -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 Ϯ 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 Ͻ 0.05) in rabbits. Fecal bile acid outputs that reflected bile acid synthesis increased 2-and 2.4-times ( P Ͻ 0.05) in cholesterol-fed rats and rabbits, respectively. Cholesterol 7 ␣ -hydroxylase activity rose 33% (24 ؎ 2.4 vs. 18 ؎ 1.6 pmol/mg/min, P Ͻ 0.01) and mRNA levels increased 50% ( P Ͻ 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 Ͻ 0.05) in rabbits. Classic bile acid synthesis (cholesterol 7 ␣hydroxylase) was inhibited in rabbits because an enlarged bile acid pool developed from enhanced ileal bile acid transport. In contrast, in rats, cholesterol 7 ␣ -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 7 ␣ -hydroxylase in rabbits. -Xu,

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“…A separate specimen of the liver was submitted for histologic examination. In the remaining half of the rabbits in each experimental group, bile drainage was continued to collect bile for 5 days, which ensured total recovery of deoxycholic acid from the bile and evaluation of the effect of bile drainage on activities of the enzymes, because after 3 days of bile drainage, cholic acid synthesis was maximally stimulated and reached a steady-state output (20). During 5 days of bile fistula, all animals were fed regular rabbit chow (without cholesterol) so that we were able to compare enzyme activities and plasma and hepatic cholesterol concentrations between rabbits with and without bile fistula but fed cholesterol for the same number of days (0, 1, 3, 5, and 10 days).…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples (2-3 ml) were taken from each rabbit immediately before and at the completion of the feeding period for determinations of plasma cholesterol concentrations and liver function tests (plasma alkaline phosphatase, glutamic-pyruvic acid transaminase, and bilirubin levels). After completion of various periods of cholesterol feeding, bile fistulas were constructed in all rabbits as described previously (20) under anesthesia (ketamine, 40 mg/kg body weight, combined with xylazine, 4 mg/kg body weight, and acepromazine, 0.5 mg/kg body weight, administered intramuscularly). Bile was collected for 30 min to determine baseline bile acid composition and percentage of deoxycholic acid in the bile.…”

Section: Methodsmentioning

confidence: 99%

Increasing dietary cholesterol induces different regulation of classic and alternative bile acid synthesis

Xu¹,

Salen²,

Shefer³

et al. 1999

J. Clin. Invest.

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Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit

Cited by 23 publications

References 16 publications

Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol

Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol

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

Increasing dietary cholesterol induces different regulation of classic and alternative bile acid synthesis

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