Editor’s Highlight: Clofibrate Decreases Bile Acids in Livers of Male Mice by Increasing Biliary Bile Acid Excretion in a PPARα-Dependent Manner

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.

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Plasma Lathosterol as a Screening Test for Bile Acid Malabsorption Due to Ileal Resection: Correlation with 75SeHCAT Test and Faecal Bile Acid Excretion

Clinical Science ◽

10.1042/cs0900315 ◽

1996 ◽

Vol 90 (4) ◽

pp. 315-319 ◽

Cited By ~ 7

Author(s):

M. A. Färkkilä ◽

K. J. Kairemo ◽

M. J. Taavitsainen ◽

T. A. Strandberg ◽

T. A. Miettinen

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Half Life ◽

Screening Test ◽

Acid Excretion ◽

Bile Acid Malabsorption ◽

Bile Acid Excretion ◽

Control Subjects ◽

Biological Half Life ◽

Schilling Test

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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BILIARY BILE ACID EXCRETION BY THE HUMAN FETUS DURING EARLY GESTATION

Pediatric Research ◽

10.1203/00006450-198704010-00660 ◽

1987 ◽

Vol 21 (4) ◽

pp. 277A-277A

Author(s):

Kenneth D R Setehell ◽

Ranjana Dumaswala ◽

Carla Colombo ◽

Fabio Sereni

Keyword(s):

Bile Acid ◽

Human Fetus ◽

Acid Excretion ◽

Early Gestation ◽

Biliary Bile Acid ◽

Bile Acid Excretion

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Bile Flow and Composition During Bile Acid Depletion and Administration

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y74-045 ◽

1974 ◽

Vol 52 (2) ◽

pp. 334-348 ◽

Cited By ~ 28

Author(s):

Curtis D. Klaassen

Keyword(s):

Bile Acid ◽

Bile Salt ◽

Bile Acids ◽

Bile Flow ◽

Enterohepatic Circulation ◽

Acid Excretion ◽

Bile Formation ◽

Bile Acid Excretion ◽

Rat Bile ◽

Acid Administration

Relatively similar concentrations of the inorganic ions were detected in rat, rabbit, and dog bile; however, dog bile had a higher concentration of protein, cholesterol, phospholipid phosphorous, and percentage solids than rat bile, and rabbit bile had the lowest concentration. The biliary excretion of bile acids was altered in each species by: (1) interruption of the enterohepatic circulation; (2) rapid administration of an exogenous load of bile acids; and (3) constant infusion of an exogenous load of bile acids. Bile acid and phospholipid phosphorous concentration and percentage solids increased after bile acid administration in all three species; however, species differences in bilirubin concentration were observed and a marked decrease was detected in rabbit and dog bile but it markedly increased in rat bile. When the enterohepatic circulation was interrupted in the dog and rat, the bile acid concentration markedly decreased with only minor changes in bile flow. This not only supports the theory that there is a bile salt independent fraction of bile formation, but also demonstrates that canalicular bile formation can be maintained at relatively normal rates with almost no excretion of bile acids. Marked discrepancy between bile acid excretion and bile flow was observed in the rat after bile acid administration, in that a marked increase in bile acid excretion was observed but little or no increase in flow. When bile flow was plotted against bile acid excretion for the three species, the slope of the line was less during bile acid administration than during depletion, indicating that the bile acids are accompanied by less water during bile acid administration than during depletion. Variation in the bile flow intercept with zero bile acid excretion (thought to represent the bile salt-independent fraction) was relatively large, which is probably due in part to alteration in the production of the bile salt independent fraction when bile acid secretion is altered. It appears that both the choleretic property of bile acids varies during various rates of bile acid excretion and the bile salt-independent fraction is not constant. Therefore, calculation of the bile salt independent fraction as previously performed should be interpreted with extreme caution. Thus, it appears difficult to determine the quantitative importance of bile acid excretion in bile formation.

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Relation between dietary cholesterol and bile acid excretion in the rat

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1962.203.6.1029 ◽

1962 ◽

Vol 203 (6) ◽

pp. 1029-1032 ◽

Cited By ~ 25

Author(s):

Jean D. Wilson

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Dietary Cholesterol ◽

Acid Synthesis ◽

Cholesterol Content ◽

Bile Acid Synthesis ◽

Fecal Excretion ◽

Acid Excretion ◽

Cholesterol Feeding ◽

Bile Acid Excretion

The influence of dietary cholesterol on fecal excretion of bile acids has been studied in rats fed isocaloric quantities of purified diets that varied only in cholesterol content. Addition of dietary cholesterol clearly resulted in an increase in excretion of total bile acids, as well as in conversion of cholesterol-4-C14 to bile acid-C14. An acceleration in bile acid excretion as a result of cholesterol feeding was demonstrated to be independent of dietary cholic acid and to occur despite suppression of the bowel flora. These results suggest that not only does absorbed dietary cholesterol play a role in determining the rate of bile acid formation but that the adaptation of bile acid synthesis to cholesterol feeding may in part be a determining factor in the varying response of different species to cholesterol feeding.

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Structurally different mixed linkage β-glucan supplements differentially increase secondary bile acid excretion in hypercholesterolaemic rat faeces

Food & Function ◽

10.1039/c8fo02507j ◽

2020 ◽

Vol 11 (1) ◽

pp. 514-523 ◽

Cited By ~ 1

Author(s):

Nunzia Iaccarino ◽

Bekzod Khakimov ◽

Mette Skau Mikkelsen ◽

Tina Skau Nielsen ◽

Morten Georg Jensen ◽

...

Keyword(s):

Molecular Structure ◽

Bile Acid ◽

Bile Acids ◽

Acid Excretion ◽

Secondary Bile Acid ◽

Bile Acid Excretion ◽

Secondary Bile Acids

This study demonstrates that structurally different barley β-glucans promote the primary and secondary bile acids’ excretion in a selective manner depending on β-glucans molecular structure.

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

British Journal Of Nutrition ◽

10.1079/bjn19890056 ◽

1989 ◽

Vol 62 (3) ◽

pp. 539-550 ◽

Cited By ~ 10

Author(s):

T. Ide ◽

M. Horii ◽

K. Kawashima ◽

T. Yamamoto

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Biliary Excretion ◽

The Other ◽

Acid Excretion ◽

Citrus Pectin ◽

Taurine Concentration ◽

Dietary Level ◽

Biliary Bile Acid ◽

Conjugated Bile Acids

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.

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Bile Acids Induce IQ Containing GTPase Activating Protein 1 to Alleviate Liver Injury

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1018 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A498-A498

Author(s):

Anushna Sen ◽

Hanna Erickson ◽

Sayeepriyadarshini Anakk

Keyword(s):

Gene Expression ◽

Bile Acid ◽

Liver Injury ◽

Bile Acids ◽

Mapk Signaling ◽

Serum Bile Acid ◽

Dependent Manner ◽

Male Mice ◽

Wild Type ◽

Junction Protein

Abstract Bile acids (BA) are cholesterol metabolites synthesized in the liver. In addition to their role as detergents, bile acids can function as signaling molecules via the activation of nuclear and G-protein coupled receptors, FXR and TGR5. BA signaling is associated with inflammation, cell proliferation, as well as apoptosis in the liver. Excessive accumulation of bile acids in the liver (cholestasis) is observed in many diseased states. We found that the scaffold protein IQGAP1 was induced in mouse models of cholestasis and in patients. In vitro BA treatment of liver cell-line, HepG2 also induced IQGAP1 in a dose-dependent manner. To investigate the role of this IQGAP1 induction, we fed wild-type male mice 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 3days, 1week, and 2weeks. Serum bile acid and hepatic IQGAP1 induction increased concomitantly with time. We next treated Iqgap1-/- male mice similarly with DDC and found a 3-fold increase in serum bile acid levels compared to treated wild-type mice. Liver injury markers ALT, AST, and bilirubin were also increased. Although Iqgap1-/- mice had similar gene expression of key BA regulators, Fxr and Shp as wild-type mice, the alteration in expression of BA transporters and reduced cell-cell junction protein levels may contribute to the elevated BAs levels. We quantified gene expression of pro-inflammatory and proliferative mediators using qRT-PCR and examined the liver histology with immuno-staining. We found Iqgap1-/- livers expressed increased pro-inflammatory mediators and proliferative genes like Il-6 and cyclin D1 along with MAPK signaling targets, Fos and Egr-1. To further examine how IQGAP1 functions as a mediator of bile acid signaling, we have generated IQGAP1 domain deleted constructs and are examining their protein-protein interactions with Mass Spec. Based on our results, IQGAP1 induction subsequent to accumulation of BAs is protective against injury in the liver.

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