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

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.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.276.3.g751 ◽

1999 ◽

Vol 276 (3) ◽

pp. G751-G760 ◽

Cited By ~ 10

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.

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Selective biliary lipid secretion at low bile-salt-output rates in the isolated perfused rat liver. Effects of phalloidin

Biochemical Journal ◽

10.1042/bj2370301 ◽

1986 ◽

Vol 237 (1) ◽

pp. 301-304 ◽

Cited By ~ 10

Author(s):

K Rahman ◽

R Coleman

Keyword(s):

Bile Salt ◽

Bile Salts ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Biliary Lipid ◽

Perfusion Fluid ◽

Lipid Secretion ◽

Rat Livers ◽

Secretion Rates ◽

Salt Secretion

At high bile-salt-secretion rates the biliary secretion of phospholipids and cholesterol is dependent on that of the bile salts. However, at low bile-salt outputs some secretion remains. Isolated perfused rat livers were used in these experiments in order to study the bile-salt-independent secretion of biliary lipids. The livers were isolated and saline (0.9% NaCl), or phalloidin dissolved in saline, was added to the perfusion fluid after 1 h of liver isolation. The concentration and output of cholesterol was significantly decreased in phalloidin-treated livers compared with the controls, whereas there was no significant decrease in phospholipids; the secretion of cholesterol and phospholipids can thus be uncoupled from each other by the action of phalloidin. These experiments suggest that a proportion of cholesterol gets into bile independently of bile salts and phospholipids. These findings are discussed in relation to the supersaturation of some biles with cholesterol and its relationship to the bile-salt-independent fraction of cholesterol.

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Triton WR-1339-induced changes in serum lipids and biliary lipid secretion

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.254.3.g346 ◽

1988 ◽

Vol 254 (3) ◽

pp. G346-G354 ◽

Cited By ~ 2

Author(s):

M. Zeniya ◽

A. Reuben

Keyword(s):

Bile Acid ◽

Serum Lipids ◽

Acid Output ◽

Serum Triglyceride ◽

Biliary Lipid ◽

Acid Transport ◽

Lipid Secretion ◽

Bile Acid Transport ◽

Triton Wr 1339 ◽

Secretion Rates

Biliary lipid secretion rates were measured in fed rats after an intravenous injection of Triton WR-1339 (TWR, 60 mg/100 g body wt), an agent that inhibits lipoprotein removal from the circulation. Serum triglyceride, phospholipid (PL), and cholesterol (CH) concentrations rose within 3 h of TWR to 45, 6.6, and 10 times control values, respectively, at 24-36 h. Serum lipids fell rapidly at 48 h and were normal by 72-96 h after TWR. TWR did not alter bile flow, hepatic bile acid transport, or biliary bile acid output. Within 0.5 h of TWR, biliary PL and CH outputs fell greater than 70%, and taurocholate-stimulated biliary PL secretion was markedly reduced. Biliary PL and CH secretion rates were approximately 30 and approximately 40% suppressed, respectively, 24 h after TWR, 160 and 330% elevated, respectively, at 48 h, and normally by 72 h, despite normal taurocholate-stimulated biliary PL secretion. Biliary beta-glucuronidase secretion (a lysosomal enzyme) was unchanged for 3 h after TWR but was increased at 24, 48, and 72 h, independent of biliary lipid secretion. Thus TWR acutely dissociates bile acid from lipid secretion without impairing bile acid transport or biliary lysosomal discharge. Late changes in biliary lipid secretion relate closely to TWR-induced change in serum lipid metabolism but not to stimulation of biliary lysosomal discharge.

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