Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis

1999 ◽  
Vol 276 (3) ◽  
pp. G751-G760 ◽  
Author(s):  
David Q.-H. Wang ◽  
Frank Lammert ◽  
David E. Cohen ◽  
Beverly Paigen ◽  
Martin C. Carey
Keyword(s):  
Cholic Acid ◽  
Bile Flow ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Absorption ◽  
Biliary Lipid ◽  
Biliary Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Lipid Secretion ◽  
Lithogenic Diet ◽  
Secretion Rates

Cholic acid is a critical component of the lithogenic diet in mice. To determine its pathogenetic roles, we fed chow or 1% cholesterol with or without 0.5% cholic acid to C57L/J male mice, which because of lith genes have 100% gallstone prevalence rates. After 1 yr on the diets, we measured bile flow, biliary lipid secretion rates, hepatic cholesterol and bile salt synthesis, and intestinal cholesterol absorption. After hepatic conjugation with taurine, cholate replaced most tauro-β-muricholate in bile. Dietary cholic acid plus cholesterol increased bile flow and biliary lipid secretion rates and reduced cholesterol 7α-hydroxylase activity significantly mostly via deoxycholic acid, cholate’s bacterial 7α-dehydroxylation product but did not downregulate cholesterol biosynthesis. Intestinal cholesterol absorption doubled, and biliary cholesterol crystallized as phase boundaries shifted. Feeding mice 1% cholesterol alone produced no lithogenic or homeostatic effects. We conclude that in mice cholic acid promotes biliary cholesterol hypersecretion and cholelithogenesis by enhancing intestinal absorption, hepatic bioavailability, and phase separation of cholesterol in bile.

Bile Lipid Secretion in Obese and Non-Obese Individuals with and without Gallstones

1985 ◽  
Vol 69 (1) ◽  
pp. 71-79 ◽  
Author(s):  
A. Reuben ◽  
P. N. Maton ◽  
G. M. Murphy ◽  
R. H. Dowling
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Biliary Lipid ◽  
Biliary Cholesterol ◽  
Cholesterol Gallstones ◽  
Lipid Secretion ◽  
Biliary Cholesterol Secretion ◽  
Cholesterol Secretion ◽  
Bile Acid Secretion ◽  
Secretion Rates

1. Biliary lipid secretion rates were measured in non-obese and obese individuals with and without cholesterol gallstones, using a steady-state, amino acid duodenal perfusion method. In addition, biliary lipid secretion rates were measured in five obese gallstone patients receiving high-dose chenodeoxycholic acid therapy (16-22 mg day−1 kg−1). 2. Bile acid secretion rates in the non-obese patients with cholesterol gallstones (563+sem 70 μmol/h, n = 6) were significantly lower than in the non-obese controls (1078 + 210 μmol/h, n = 10, P < 0.05), whereas cholesterol secretion rates were similar in the non-obese individuals with and without gallstones (51+7 and 42+4 μmol/h respectively). 3. In the obese, both with and without gallstones, the major abnormality was hypersecretion of cholesterol (107+7 μmol/h, n = 7, and 81 + 15 μmol/h, n = 7, respectively). Both these values were significantly greater than those in the non-obese controls (P < 0.01-0.02). 4. Biliary cholesterol secretion rates correlated significantly with bile acid secretion rates but, for every mole of bile acid secreted, the obese secreted more cholesterol than the non-obese. 5. Chenodeoxycholic acid treatment lowered biliary cholesterol saturation in obese gallstone patients by reducing biliary cholesterol secretion. 6. These results suggest that there are two major types of defect in biliary lipid secretion in gallstone patients: reduced biliary bile acid secretion in non-obese gallstone patients and excessive biliary cholesterol secretion in the obese.

Mechanism for Biliary Cholesterol Supersaturation: Biliary Lipid Secretion Studies in Obesity with and without Gallstones

1979 ◽  
Vol 56 (3) ◽  
pp. 22P-22P ◽  
Author(s):  
A. Reuben ◽  
P. N. Maton ◽  
Y. Quereshi ◽  
R. H. Dowling
Keyword(s):  
Biliary Lipid ◽  
Biliary Cholesterol ◽  
Lipid Secretion

Differing effects of norcholate and cholate on bile flow and biliary lipid secretion in the rat

1984 ◽  
Vol 246 (1) ◽  
pp. G67-G71
Author(s):  
E. R. O'Maille ◽  
S. V. Kozmary ◽  
A. F. Hofmann ◽  
D. Gurantz
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Unit Increase ◽  
Cholesterol Secretion ◽  
Bile Acid Secretion

The effects of norcholate (a C23 bile acid that differs from cholate in having a side chain containing four rather than five carbon atoms) on bile flow and biliary lipid secretion were compared with those of cholate, using the anesthetized rat with a bile fistula. Norcholate and cholate were infused intravenously over the range of 0.6-6.0 mumol X min-1 X kg-1. Both bile acids were quantitatively secreted into bile; norcholate was secreted predominantly in unconjugated form in contrast to cholate, which was secreted predominantly as its taurine or glycine conjugates. The increase in bile flow per unit increase in bile acid secretion induced by norcholate infusion [17 +/- 3.2 (SD) microliters/mumol, n = 8] was much greater than that induced by cholate infusion (8.6 +/- 0.9 microliters/mumol, n = 9) (P less than 0.001). Both bile acids induced phospholipid and cholesterol secretion. For an increase in bile acid secretion (above control values) of 1 mumol X min-1 X kg-1, the increases in phospholipid secretion [0.052 +/- 0.024 (SD) mumol X min-1 X kg-1, n = 9] and cholesterol secretion (0.0071 +/- 0.0033 mumol X min-1 X kg-1, n = 9) induced by norcholate infusion were much less than those induced by cholate infusion (0.197 +/- 0.05 mumol X min-1 X kg-1, n = 9, and 0.024 +/- 0.011 mumol X min-1 X kg-1, n = 9, respectively; P less than 0.001 for both phospholipid and cholesterol). The strikingly different effects of norcholate on bile flow and biliary lipid secretion were attributed mainly to its possessing a considerably higher critical micellar concentration than cholate.

Effect of cholestyramine treatment on biliary lipid secretion rates in normolipidaemic men

1991 ◽  
Vol 229 (3) ◽  
pp. 241-246 ◽  
Author(s):  
M. CARRELLA ◽  
S. ERICSSON ◽  
C. PIANO ◽  
B. ANGELIN ◽  
K. EINARSSON
Keyword(s):  
Biliary Lipid ◽  
Lipid Secretion ◽  
Secretion Rates

Role of intestinal sterol transporters Abcg5, Abcg8, and Npc1l1 in cholesterol absorption in mice: gender and age effects

2006 ◽  
Vol 290 (2) ◽  
pp. G269-G276 ◽  
Author(s):  
Li-Ping Duan ◽  
Helen H. Wang ◽  
Akira Ohashi ◽  
David Q.-H. Wang
Keyword(s):  
Molecular Mechanisms ◽  
Apical Membrane ◽  
Cholesterol Absorption ◽  
Absorption Efficiency ◽  
Biliary Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Gender And Age ◽  
Multistep Process ◽  
17Β Estradiol

Recent studies have indicated that intestinal cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. However, the molecular mechanisms whereby there are gender differences in intestinal cholesterol absorption efficiency and the efficiency of cholesterol absorption increases with age have not yet been fully understood. To explore whether aging increases cholesterol absorption via intestinal sterol transporters, we studied the higher cholesterol-absorbing C57L/J vs. the lower cholesterol-absorbing AKR/J mice at 8 (young adult), 36 (older adult), and 50 (aged) wk of age. To test the hypothesis that estrogen receptor (ER )α plays an important regulatory role in cholesterol absorption, we investigated the gonadectomized mice of both genders treated with 17β-estradiol-releasing pellets at 0, 3, or 6 μg/day and antiestrogenic ICI 182,780 at 125 μg/day. We found that hepatic outputs of biliary cholesterol were significantly increased with age and in response to high levels of estrogen. Aging significantly enhances cholesterol absorption by suppressing expression of the jejunal and ileal sterol efflux transporters [ATP-binding cassette ( Abc) g5 and Abcg8] and upregulating expression of the putative duodenal and jejunal sterol influx transporter Npc1l1. Estrogen significantly augmented cholesterol absorption mostly due to an upregulated expression of intestinal Npc1l1, Abcg5, and Abcg8 via the intestinal ERα pathway, which can be fully abolished by the antagonist. We conclude that ERα activated by estrogen and aging enhances cholesterol absorption by increasing biliary lipid output and mediating intestinal sterol transporters favoring influx of intraluminal cholesterol molecules across the apical membrane of the enterocyte.

Effect of simvastatin, ursodeoxycholic acid and simvastatin plus ursodeoxycholic acid on biliary lipid secretion and cholic acid kinetics in nonfamilial hypercholesterolemia

Hepatology ◽  
1992 ◽  
Vol 15 (6) ◽  
pp. 1072-1078 ◽  
Author(s):  
Giuseppe Mazzella ◽  
Paolo Parini ◽  
Davide Festi ◽  
Franco Bazzoli ◽  
Rita Aldini ◽  
...  
Keyword(s):  
Ursodeoxycholic Acid ◽  
Cholic Acid ◽  
Biliary Lipid ◽  
Lipid Secretion

scholarly journals Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse

1996 ◽  
Vol 314 (3) ◽  
pp. 781-786 ◽  
Author(s):  
José CHIANALE ◽  
Valeska VOLLRATH ◽  
Ana M. WIELANDT ◽  
Ludwig AMIGO ◽  
Attilio RIGOTTI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Flow ◽  
Control Group ◽  
Biliary Lipid ◽  
Membrane Domain ◽  
Lipid Secretion ◽  
Pharmacological Modulation ◽  
P Glycoprotein ◽  
Liver Gene ◽  
Plasma Membrane Domain

Disruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids. We tested the hypothesis that the increase in biliary phospholipid output induced by fibrates is mediated via induction of the hepatic mdr2 gene and its encoded product, the P-glycoprotein canalicular flippase. Increased levels of mdr2 mRNA were observed in the liver of mice treated with different fibrates: ciprofibrate, 660±155% (as compared with control group); clofibrate, 611±77%; bezafibrate, 410±47%; fenofibrate, 310±52%; gemfibrozil, 190±25% (P < 0.05 compared with control group). Induction of expression of the mdr gene family was specific to the mdr2 gene. Two- to three-fold increases in P-glycoprotein immunodetection were evident on the canalicular plasma-membrane domain of clofibrate- and ciprofibrate-treated mice. Biliary phospholipid output increased from 4.2±1.2 nmol/min per g of liver in the control group to 8.5±0.6, 7.1±2.9 and 5.8±2.5 in ciprofibrate-, clofibrate- and bezafibrate-treated mice respectively (P < 0.05 compared with control group). Moreover, a significant correlation between biliary phospholipid output and the relative levels of mdr2 mRNA was found (r = 0.86; P < 0.05). In treated animals, bile flow as well as cholesterol and bile acid outputs remained unchanged. Our findings constitute the first evidence that pharmacological modulation of biliary lipid secretion mediated by fibrates can be related to the overexpression of a specific liver gene product, the mdr2 P-glycoprotein, and are consistent with the hypothesis that the mdr2 P-glycoprotein isoform plays a crucial role in the secretion of biliary phospholipid.

scholarly journals Impaired response of biliary lipid secretion to a lithogenic diet in phosphatidylcholine transfer protein-deficient mice

2004 ◽  
Vol 46 (3) ◽  
pp. 422-431 ◽  
Author(s):  
Michele K. Wu ◽  
Hideyuki Hyogo ◽  
Suresh K. Yadav ◽  
Phyllis M. Novikoff ◽  
David E. Cohen
Keyword(s):  
Biliary Lipid ◽  
Lipid Secretion ◽  
Lithogenic Diet ◽  
Transfer Protein ◽  
Phosphatidylcholine Transfer Protein ◽  
Deficient Mice
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