Active absorption of conjugated bile acids in vivo

Marcus, Samuel F.; Schteingart, Claudio D.; Marquez, Mario L; Hofmann, Alan F.; Xia, Yun; Steinbach, Joseph H.; Ton-Nu, Huong-Tu; Lillienau, Jan; Angellotti, M. A.; Schmassmann, Adrian

doi:10.1016/0016-5085(91)90603-i

Cited by 50 publications

(2 citation statements)

References 39 publications

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“…Perhaps more interestingly, the remnant pool of enterohepatically circulating BAs in Asbt-deficient mice displayed increased α-diversity, compared with wild type controls, and was compositionally indistinguishable from both wild type and Asbt-deficient fecal pools (Figure 2A-C). At the species level, reshaping of the enterohepatic BA pool in Asbt-deficient mice was due to the depletion of virtually all 1 o cBAs and 1 o uBAs -consistent with previous ideas that 1 o cBAs are preferred Asbt transport substrates in the ileum 44 -and concomitant increases in 2 o uBAs and metabolites normally enriched in the LI (Figure 2D). These results suggest that Asbt-mediated ileal BA absorption sustains both the unique size and composition of the enterohepatic BA pool.…”

Section: Asbt-deficiency Reveals Interconnected Response Network Unde...supporting

confidence: 90%

“…The estimate that ~95% of all BAs are absorbed in the ileum stems from classical studies in which small intestines of experimental animals were perfused with individual BAs, or human volunteers were dosed orally, and serum levels were followed over time to estimate absorption 44,[62][63][64][65][66][67][68][69][70] . However, as each BA species possesses unique pharmacokinetic properties, including rates and routes of intestinal absorption 71,72 , this general estimate cannot be uniformly applied to complex BA pools.…”

Section: Quantifying Ileal Ba Absorption In Vivomentioning

confidence: 99%

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Quantifying forms and functions of intestinal bile acid pools in mice

Sudo,

Delmas-Eliason,

Soucy

et al. 2024

Preprint

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Bile acids (BAs) are gastrointestinal metabolites that serve dual functions in lipid absorption and cell signaling. BAs circulate actively between the liver and distal small intestine (i.e., ileum), yet the dynamics through which complex BA pools are absorbed in the ileum and interact with intestinal cells in vivo remain ill-defined. Through multi-site sampling of nearly 100 BA species in individual wild type mice, as well as mice lacking the ileal BA transporter, Asbt/Slc10a2, we calculate the ileal BA pool in fasting C57BL/6J mice to be ~0.3 μmoles/g. Asbt-mediated transport accounts for ~80% of this pool and amplifies size, whereas passive absorption explains the remaining ~20%, and generates diversity. Accordingly, ileal BA pools in mice lacking Asbt are ~5-fold smaller than in wild type controls, enriched in secondary BA species normally found in the colon, and elicit unique transcriptional responses in cultured ileal explants. This work quantitatively defines ileal BA pools in mice and reveals how BA dysmetabolism can impinge on intestinal physiology.

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Section: Asbt-deficiency Reveals Interconnected Response Network Unde...supporting

confidence: 90%

Section: Quantifying Ileal Ba Absorption In Vivomentioning

confidence: 99%

Quantifying forms and functions of intestinal bile acid pools in mice

Sudo,

Delmas-Eliason,

Soucy

et al. 2024

Preprint

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N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: Effects of acute feeding in the rat

et al. 1995

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The purpose of this study was to investigate the physicochemical/biological properties and the effects of acute administration of N-ethyl-tauroursodeoxycholic acid in bile-fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning, cholesterol solubilizing capacity, and sensitivity to enzyme deconjugation by bacteria and cholylglycine-hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow, lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-tauroursodeoxycholate has a lipophilicity slightly higher than tauroursodeoxycholate, close to taurocholate, and similar cholesterol solubilizing capacity. Deconjugation of N-ethyl-tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for tauroursodeoxycholate). The two bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater lipid secretion than tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two bile salts were recovered in bile. No unconjugated bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

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Fluorescent bile acid derivatives: Relationship between chemical structure and hepatic and intestinal transport in the rat

Holzinger¹,

Schteingart²,

Ton‐Nu³

et al. 1997

Hepatology

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Studies were performed to characterize hepatic and intestinal transport, as well as biotransformation during transport, of a spectrum of fluorescent bile acids containing a fluorophore attached to the side chain. The following two classes of compounds were studied: 1) aminofluorescein (amF) coupled directly to the carboxylic group of a bile acid which was cholic, ursodeoxycholic, or cholylglycine; and 2) nitrobenzoxadiazolyl (NBD) coupled to the epsilon-amino group of a lysine conjugated bile acid, which was cholic or ursodeoxycholic. Fluorescein, a cholephilic organic anion, was studied as a control. Fluorescent bile acids were synthesized and their structures confirmed by nuclear magnetic resonance and mass spectrometry. Using the biliary fistula rat, hepatic transport, biotransformation, and choleretic activity were defined; intestinal absorption was assessed by jejunal or ileal perfusion studies. All fluorescent bile acids had hepatic transport maxima about one-sixth that reported for cholyltaurine, but derivatives of cholylglycine were transported best. Bile acids underwent little (<5%) biotransformation during hepatocyte transport. Only the amF conjugate of cholylglycine had normal choleretic activity; other compounds were hypocholeretic or cholestatic. In contrast, fluorescein was well transported, was partly glucuronidated, and had normal choleretic activity. NBD-tagged, but not amF-tagged, bile acids were actively transported by the intestine (ileum > jejunum), and no fluorescent bile acid had passive intestinal permeability; NBD-tagged bile acids were biotransformed during intestinal transport (jejunum > ileum). We conclude that the structure of the fluorophore as well as that of the bile acid influences transport by the hepatocyte and enterocyte. These fluorescent bile acids differ from fluorescein in being impermeable to cell membranes and undergoing little biotransformation during hepatocyte transport. Of these fluorescent bile acids, cholylglycylamF has hepatocyte transport and choleretic properties most closely resembling those of a natural bile acid.

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Active absorption of conjugated bile acids in vivo

Cited by 50 publications

References 39 publications

Quantifying forms and functions of intestinal bile acid pools in mice

Quantifying forms and functions of intestinal bile acid pools in mice

N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: Effects of acute feeding in the rat

Fluorescent bile acid derivatives: Relationship between chemical structure and hepatic and intestinal transport in the rat

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