scholarly journals Bile acid conjugation and hepatic taurine concentration in rats fed on pectin

1989 ◽  
Vol 62 (3) ◽  
pp. 539-550 ◽  
Author(s):  
T. Ide ◽  
M. Horii ◽  
K. Kawashima ◽  
T. Yamamoto

A relationship between bile acid conjugation and hepatic taurine concentration was investigated in rats fed on citrus pectin. When rats were fed on the diets containing varying amounts of pectin (10, 30, 60 and 100 g/kg dietary levels), biliary excretion of bile acids increased as the dietary levels of pectin increased. The increase was entirely due to the glycine-conjugated bile acids. The biliary excretion of taurine-conjugated bile acid was somewhat decreased as the dietary level of the fibre increased. Consequently, most of the bile acids were conjugated with glycine in rats fed on the diet containing 100 g pectin/kg. On the other hand, dietary cellulose (60 and 100 g/kg) did not affect the biliary bile acid excretions. The major proportion of bile acids in rats receiving a fibre-free diet and the diets containing cellulose were conjugated with taurine. Hepatic taurine concentrations decreased as the dietary levels of pectin, but not of cellulose, increased. Although dietary pectin (100 g/kg) also slightly decreased the taurine concentration in the kidney, those concentrations in other non-hepatic tissues examined (heart, brain and serum) were unaffected by the dietary fibre. Supplementation of the diet containing 100 g pectin/kg with methionine (10 g/kg) and taurine (10 and 50 g/kg) strikingly increased hepatic taurine concentrations. In this situation, the conjugation of bile acid with glycine was almost abolished and taurine conjugates became abundant in the bile of these animals. It is suggested that dietary pectin mediated an increase in the biliary bile acid excretion which may have depleted the hepatic pool of taurine available for bile acid conjugation and, thus, increased glycine conjugation of bile acids.

1963 ◽  
Vol 43 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Kjell Hellström ◽  
Ove Strand

ABSTRACT Bile fistula bile from male normal, sham-operated, adrenalectomized and cortisone substituted adrenalectomized rats was analyzed for free and conjugated bile acids. 40–50 per cent of the bile acids from adrenalectomized rats were conjugated with glycine as compared to less than 10 per cent in the other groups. The cortisone substituted adrenalectomized rats showed a lower glycine conjugation than normal rats. In the bile from adrenal-ectomized rats, free cholic acid corresponding to 2–5% of the conjugated bile acids was detected. In the bile from the other groups less than 1% of free cholic acid was found. The mechanism responsible for the abnormal conjugation pattern found in adrenalectomized rats is discussed.


1989 ◽  
Vol 61 (3) ◽  
pp. 545-557 ◽  
Author(s):  
T. Ide ◽  
M. Horii

1. Bile acids were analysed in the bile and lumen samples of rats which received a cholesterol-free or cholesterol-enriched (5 g/kg) diet free from fibre, or containing cellulose or citrus pectin at the level of 100 g/kg.2. Dietary pectin but not cellulose increased biliary bile acid concentration and excretion. Dietary cholesterol did not affect biliary bile acids quantitatively.3. Biliary bile acids were almost exclusively conjugated with glycine or taurine in the various experimental situations. The predominant portion of bile acids in rats fed on the cholesterol-free diet was conjugated with taurine when the diet was either free from fibre or contained cellulose; the ratio of bile acids conjugated with glycine: those conjugated with taurine (G:T) was less than 0·2. In contrast, with pectin as a fibre source, the conjugation with glycine increased enormously (G:T increased to approximately 4). Cholesterol enrichment of the diet also increased the glycine conjugation in all groups of rats. Even in this situation, the G:T was highest in rats fed on pectin.4. Pectin, but not cellulose, increased the bile acid content of the small intestine and caecum, both in rats fed on the cholesterol-free and cholesterol-enriched diets. Cholesterol feeding doubled the bile acid content of the caecum in rats fed on a fibre-free diet or a cellulose diet, but not in those fed on pectin. No such effect of cholesterol was observed in the small intestine, except for the ileal bile acid content in rats fed on cellulose.5. A considerable portion of the bile acids in the small intestine was deconjugated. The extent of the deconjugation was higher in the ileum than in the jejunum. As in the bile, G:T in rats fed on pectin (3·5·5) were higher than those in the other groups (0·05–1·05) in various situations. Also, cholesterol feeding considerably increased the ratio in all groups of rats.6. The observed dietary alteration of the partition of bile acids between glycine and taurine may be of physiological significance in regulating bile acid and lipid metabolism in rats.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Thomas Q de Aguiar Vallim ◽  
Elizabeth J Tarling ◽  
Hannah Ahn ◽  
Lee R Hagey ◽  
Casey E Romanoski ◽  
...  

Elevated circulating cholesterol levels is a major risk factor for cardiovascular diseases (CVD), and therefore understanding pathways that affect cholesterol metabolism are important for potential treatment of CVD. The major route for cholesterol excretion is through its catabolism to bile acids. Specific bile acids are also potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis ( Cyp7a1 , Cyp8b1 ) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway, and modifies the biliary bile acid composition. In contrast, MafG loss-of-function studies cause de-repression of the bile acid genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-Seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR. The identification of this pathway will likely have important implications in metabolic diseases.


2017 ◽  
Vol 35 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Davor Slijepcevic ◽  
Stan F.J. van de Graaf

Background: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.


1973 ◽  
Vol 45 (3) ◽  
pp. 403-406
Author(s):  
R. A. Smallwood ◽  
P. Jablonski ◽  
J. McK. Watts

1. [14C]Cholesterol was administered intravenously via the umbilical vein to foetal sheep in the latter half of gestation, and the incorporation of radioactive label into foetal bile acids was assessed. 2. After 4 days, 0·5–2% of the radioactive label was found in foetal bile. Seventy to eighty per cent of the radioactive label in foetal bile was present as [14C]taurocholic acid and [14C]taurochenodeoxycholic acid. The remainder was [14C]cholesterol. No radioactive label was found in taurodeoxycholic acid, or in any of the glycine-conjugated bile acids. 3. It is concluded that the foetal sheep liver in the second half of gestation synthesizes taurocholic acid and taurochenodeoxycholic acid. However, the secondary bile acid taurodeoxycholic acid and the glycine-conjugated bile acids, present in foetal bile, have been acquired by placental transfer from the mother.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 317-318
Author(s):  
Renan Antunes Donadelli ◽  
Julia G Pezzali ◽  
Patrícia M Oba ◽  
Kelly S Swanson ◽  
Craig N Coon ◽  
...  

Abstract In 2018 the Food and Drug Administration (FDA) released a statement that grain-free diets may be related to the increased incidence of dilated cardiomyopathy (DCM) in dogs. This statement was made despite all implicated diets meeting nutrient requirements published by the Association of American Feed Controls Official (AAFCO) and enforced by State Officials. Many of these dogs presented with low plasma or whole blood taurine concentrations, and as such, we hypothesized that feeding these diets would result in reduced taurine status over a 26 wk feeding period. The objective of this study was to determine the effects of feeding a grain-free diet to large breed dogs on taurine status and overall health. Eight Labrador Retrievers (4 males, 4 females; Four Rivers Kennel, MO) were individually housed and fed a commercial complete and balanced grain-free diet (Acana Pork and Squash formula; APS; moisture 8.40%, crude protein 37.81%, crude fat 18.78%, ash 8.06%, and total dietary fiber 11.40%) for 26 weeks. Fasted blood samples were collected at week 0 and 26 for analyses of plasma and whole blood taurine. Urine was collected by free catch and analyzed for taurine and creatinine. Fresh fecal samples were collected and analyzed for bile acids. Data were analyzed using the GLIMMIX procedure with repeated measures in SAS (v. 9.4). Dogs were healthy throughout the duration of the trial. Urinary taurine to creatinine ratio did not change throughout the feeding period (wk 0 = 0.25 vs. wk 26 = 0.28). Fecal bile acid excretion increased after 26 weeks of feeding APS to dogs. Despite the higher fecal excretion of bile acids, plasma and whole blood taurine increased over the 26 wk feeding period. In conclusion, feeding APS for 26 wk results in increased taurine status in large breed dogs, despite higher excretion of fecal bile acids.


1996 ◽  
Vol 90 (4) ◽  
pp. 315-319 ◽  
Author(s):  
M. A. Färkkilä ◽  
K. J. Kairemo ◽  
M. J. Taavitsainen ◽  
T. A. Strandberg ◽  
T. A. Miettinen

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids<10 mg day−1 kg−1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day−1 kg−1, n = 13). 3. Faecal bile acid excretion was 5.9 ± 1.0 mg day−1 kg−1 in control subjects and 45.7 ± 6.1 mg day−1 kg−1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T½) was 95.6 ± 16.3 h and 14.1 ± 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 ± 84 μg/ml compared with 400 ± 59 μg/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P<0.001), with 75SeHCAT T½ (r = −0.524, P<0.05) and with Schilling test (r = −0.591, P<0.05). Significant correlations were also obtained for Δ8-cholestenol with faecal bile acids (r = 0.784, P<0.001) and 75SeHCAT (r = −0.505, P<0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = −0.702, P<0.01). Using mean + 2 SD of lathosterol (In μg/ml cholesterol) as a cut-off value and 10 mg day−1 kg−1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.


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