Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

Stange, Eduard F.; Scheibner, Jürgen; Ditschuneit, H.

doi:10.1172/jci114137

Cited by 61 publications

(34 citation statements)

References 53 publications

(39 reference statements)

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“…Biliary cholesterol secretion in hamsters, as shown previously for rats, 10,42 increased during bile acid infusions as a function of the bile acid hydrophobicity and the transhepatic bile acid flux, but independent of the cholesterol source. Under physiological conditions (6-9 hours), biliary secretion of de novo cholesterol amounted to no more than 18% in rats 45,47,55,56 and 5% in hamsters and humans.…”

Section: Discussionsupporting

confidence: 74%

“…Therefore, the presence of deoxycholate during a high-dose cholate infusion may be required for a long-term control of bile acid synthesis. Support comes from studies in rats 10 in which physiological amounts of deoxycholate together with taurocholate were able to control cholate formation. However, it is impossible to exclude that it was the high dose of cholate alone that regulated synthesis of both primary bile acids in hamsters.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is impossible to exclude that it was the high dose of cholate alone that regulated synthesis of both primary bile acids in hamsters. Infusion experiments in rats 10 coordinate down-regulation of cholesterol 7␣-and 27-hydroxylase [36][37][38] has been proposed for the rat, although this has not been confirmed consistently, 35 and species differences may also influence the results. 39 With respect to long-term effects on synthesis from de novo cholesterol, the infusion of conjugated cholate in a low dose and of deoxycholate in a high dose increased the amount of cholate synthesis from de novo cholesterol, most likely mediated by its increased availability, whereas de novo proportions of chenodeoxycholate remained unchanged.…”

Section: Discussionmentioning

confidence: 99%

“…3 It was traditionally assumed that primary bile acids alone mediate a negative feedback control, 4,5 but this is not consistent with negative experiments in cell culture, [6][7][8] as well as in vivo in the rat. [9][10][11][12] Thus, we suggested that the more hydrophobic secondary bile acids may be more effective than the primary bile acids. 10 In general, with increasing hydrophobicity, bile acids gain a higher capacity to suppress bile acid synthesis 13 in cultured hepatoma cells, [14][15][16] experimental animals, 10,13,17,18 and humans.…”

mentioning

confidence: 99%

“…[9][10][11][12] Thus, we suggested that the more hydrophobic secondary bile acids may be more effective than the primary bile acids. 10 In general, with increasing hydrophobicity, bile acids gain a higher capacity to suppress bile acid synthesis 13 in cultured hepatoma cells, [14][15][16] experimental animals, 10,13,17,18 and humans. 19,20 Therefore, an increased intestinal formation of secondary bile acids during expansion of the primary bile acid pool could result in a decreased hepatic formation of primary bile acids.…”

mentioning

confidence: 99%

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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: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 1999

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Bile acids exert negative feedback control on bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7α-hydroxylase activity

Kwekkeboom¹,

Princen²,

Voorthuizen³

et al. 1990

Hepatology

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Feedback regulation of bile acid synthesis by its end products was studied in cultured hepatocytes of young weaned pigs. We previously showed that conversion of exogenous [14C] cholesterol into bile acids was suppressed by addition of bile acids to the culture medium. In the present study, the effects of bile acids on bile acid mass production and cholesterol 7 alpha-hydroxylase activity were examined. Mass production of bile acids was strongly inhibited by addition of taurocholic acid (50 and 100 mumol/L) to the culture medium. The inhibitory action was exerted specifically on activity of cholesterol 7 alpha-hydroxylase because conversion of [14C] 7 alpha-hydroxycholesterol to bile acids by pig hepatocytes was not affected. Suppression of cholesterol 7 alpha-hydroxylase activity after incubation of the hepatocytes with taurocholic acid was concentration- and time-dependent. Maximum suppression (-80%) was achieved after a 20 to 30 hr incubation of hepatocytes with 100 mumol/L of this bile acid. Decline of enzyme activity caused by 100 mumol/L taurocholic acid followed first-order kinetics with a half-life of 10 hr. Taurocholic acid had no direct effect on cholesterol 7 alpha-hydroxylase activity in homogenates of hepatocytes as assessed by addition of the bile acid to the assay mixture. The effects of several other bile acids in a concentration of 100 mumol/L on cholesterol 7 alpha-hydroxylase activity were examined in 48 hr incubations. Glycochenodeoxycholic and glycohyodeoxycholic acids, which are the major bile acids in pig bile, their unconjugated forms and also deoxycholic and cholic acid pronouncedly inhibited activity of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

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Regulation of bile acid synthesis

1991

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Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

Cited by 61 publications

References 53 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

Bile acids exert negative feedback control on bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7α-hydroxylase activity

Regulation of bile acid synthesis

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