Pretreatment Biliary Lipid Composition in White Patients with Radiol0ucent Gallstones in the National Cooperative Gallstone Study

Hofmann, Alan F.; Grundy, Scott M.; Lachin, John M.; Lan, Shu-Ping; Baum, Richard A.; Hanson, Russell F.; Hersh, Theodore; Hightower, Nicholas C.; Marks, Jay W.; Mekhjian, Hagop S.; Shaefer, Robert A.; Soloway, Roger D.; Thistle, Johnson L.; Thomas, Fred B.; Tyor, Malcolm P.

doi:10.1016/s0016-5085(82)80002-4

Cited by 102 publications

(22 citation statements)

References 49 publications

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“…As reported earlier, 8,23 gallstone-susceptible mice fed the lithogenic diet showed a relative hypersecretion of cholesterol compared with phospholipids and bile acids, which allows bile to become lithogenic. Because gallstone patients also exhibit elevated cholesterol/phospholipid ratios, 35 altered molecular mechanisms of biliary lipid secretion in mice may indeed reflect similar changes in humans.…”

Section: Discussionmentioning

confidence: 99%

Biliary Cholesterol Hypersecretion in Gallstone–Susceptible Mice Is Associated With Hepatic Up–Regulation of the High–Density Lipoprotein Receptor Srbi

Fuchs¹,

Ivandic

Müller³

et al. 2001

Hepatology

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Enhanced hepatocellular trafficking of cholesterol to the bile canaliculus and cholesterol hypersecretion appears critical for gallstone formation. Therefore, we studied in more detail the hepatic cholesterol transport pathways in a mouse model of cholesterol gallstone disease. Biliary lipid secretion rates, plasma lipoprotein levels, hepatic expression of lipoprotein receptors, lipid regulatory enzymes, and putative cholesterol transporting proteins were analyzed in gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice, which were fed a lithogenic diet. Biliary cholesterol hypersecretion in C57L mice was associated with decreased plasma high-density lipoprotein (HDL) cholesterol levels and significant hepatic induction of the HDL receptor (SRBI) and cholesteryl ester hydrolase. In response to the lithogenic diet, fatty-acid binding protein of liver (FABPL) was markedly induced in both mouse strains. Caveolin 1 was elevated only in plasma membranes of gallstone-susceptible C57L mice, which also failed to down-regulate cholesterol synthesis. These data suggest a role of the reverse cholesterol transport pathway for genetically determined gallstone susceptibility in the mouse. (HEPATOLOGY 2001;33: 1451-1459.)

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Section: Discussionmentioning

confidence: 99%

Biliary Cholesterol Hypersecretion in Gallstone–Susceptible Mice Is Associated With Hepatic Up–Regulation of the High–Density Lipoprotein Receptor Srbi

Fuchs¹,

Ivandic

Müller³

et al. 2001

Hepatology

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“…They found that bile acid secretion increased, whereas the biliary secretion rates of cholesterol and phospholipids were unchanged. Some authors have reported on a positive correlation between the percentage of biliary DCA and the molar percentage of biliary cholesterol and cholesterol saturation of bile in gallstone patients and gallstone-free subjects [31,35]. Other authors have not found any correlation between cholesterol saturation and the percentage of DCA [60,61].…”

Section: Discussionmentioning

confidence: 99%

Deoxycholic acid treatment in patients with cholesterol gallstones: failure to detect a suppression of cholesterol 7α‐hydroxylase activity

Hillebrant¹,

Nyberg²,

Angelin³

et al. 1999

Journal of Internal Medicine

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Abstract. Hillebrant C-G, Nyberg B, Angelin B, Axelson M, Bjo Èrkhem I, Rudling M, Einarsson C (Huddinge University Hospital and Karolinska Hospital, Karolinska Institute, Stockholm, Sweden). Deoxycholic acid treatment in patients with cholesterol gallstones: failure to detect a suppression of cholesterol 7a-hydroxylase activity. J Intern Med 1999; 246: 399±407.Objectives. Based on animal studies, hydrophobic bile acids have been postulated to be particularly strong inhibitors of bile acid synthesis. The present study was undertaken to characterize in humans the effects of one of the most hydrophobic of the common bile acids, deoxycholic acid (DCA), on the transcriptional regulation and activity of the cholesterol 7a-hydroxylase, on hepatic cholesterol metabolism and on biliary lipid metabolism and plasma lipids. Design, subjects and settings. Thirteen patients with cholesterol gallstone disease were treated with DCA (750 mg day 21 ) for 3 weeks prior to cholecystectomy. Blood samples were collected before and during treatment. At operation, a liver biopsy and gallbladder bile were obtained. Twenty-eight untreated gallstone patients undergoing cholecystectomy served as controls. The study was carried out at a university hospital. Results. Deoxycholic acid comprised 72 6 6% (mean 6 SEM) of total biliary bile acids in DCAtreated patients (n = 8), and 21 6 2% in the controls (n = 16; P , 0.001). Cholesterol saturation of gallbladder bile averaged 102% in both treated (n = 7) and untreated (n = 16) patients. Cholesterol 7a-hydroxylase and HMG CoA reductase activities and mRNA levels were not different between DCA-treated and untreated gallstone patients. The LDL receptor mRNA levels were similar in both groups of patients. Plasma levels of total cholesterol were lowered by 10% upon DCA treatment (P , 0.05). Conclusions. Treatment with DCA did not significantly affect mRNA levels and activity of hepatic cholesterol 7a-hydroxylase or HMG CoA reductase in patients with cholesterol gallstones. There was no effect on the saturation of gallbladder bile, Thus, the present study could not verify that the hydrophobicity of the bile acid pool is a major factor regulating human hepatic cholesterol 7a-hydroxylase activity.

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“…Biliary secretion of cholesterol and phospholipids depends in part on the hydrophobicity of the bile acid pool [ 181. Deoxycholic acid is the most detergent of the main bile acids in human bile, it causes the highest secretion of both cholesterol and phospholipids in bile [18] and might play a role in the pathogenesis of cholesterol gallstone formation [ 19,201. Our patients had a significant reduction in the percent deoxycholic acid, which may further explain the reduction in the cholesterol mass within the gallbladder.…”

Section: Discussionmentioning

confidence: 99%

Effect of colectomy with ileo‐anal anastomosis on the biliary lipids

Galatola¹,

Fracchia²,

Jazrawi

1995

Eur J Clin Investigation

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Total colectomy with ileo-anal anastomosis is an effective treatment for ulcerative colitis and familial adenomatous polyposis. The absence of the colon and the coexistence of bile acid malabsorption may increase bile lithogenicity, but data on biliary lipid composition in patients with this operation is lacking. Our aim was to assess bile lithogenicity, bile composition and mass of biliary lipids within the gallbladder. We studied 11 patients with total colectomy and ileo-anal anastomosis and 16 healthy controls. We measured the percentage composition of conjugated bile acids and the masses within the gallbladder of the three main biliary lipids. This method, in contrast with measurement of cholesterol saturation index, can determine the cause of bile lithogenicity in terms of absolute modifications of the biliary lipids. There was no difference in the cholesterol saturation index between patients and controls. Colectomy patients had reduced masses of all three biliary lipids (medians and ranges, mmol): cholesterol 0.11 (0.03-0.24) vs. 0.36 (0.02-0.96), P < 0.02; bile acid 1.62 (0.75-5.21) vs. 3.95 (1.27-8.70), P < 0.01; phospholipids 0.35 (0.07-0.69) vs. 1.14 (0.14-3.00), P < 0.002. They also had reduced per cent deoxycholic acid: 3.8 (0.0-27.6) vs. 17.4 (6.4-44.7), P < 0.005, and increased percent cholic acid: 44.9 (23.3-71.4) vs. 34.3 (19.2-57.9), P < 0.05. We conclude that, despite having bile acid malabsorption, patients with colectomy and ileo-anal anastomosis have a normal cholesterol saturation index, caused by a concomitant reduction in the masses of all three biliary lipids. The reduced per cent biliary deoxycholic acid may help explain the reduced cholesterol and phospholipid masses in these patients. Total colectomy with ileo-anal anastomosis does not seem to predispose to the formation of cholesterol gallstones.

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Pretreatment Biliary Lipid Composition in White Patients with Radiol0ucent Gallstones in the National Cooperative Gallstone Study

Cited by 102 publications

References 49 publications

Biliary Cholesterol Hypersecretion in Gallstone–Susceptible Mice Is Associated With Hepatic Up–Regulation of the High–Density Lipoprotein Receptor Srbi

Biliary Cholesterol Hypersecretion in Gallstone–Susceptible Mice Is Associated With Hepatic Up–Regulation of the High–Density Lipoprotein Receptor Srbi

Deoxycholic acid treatment in patients with cholesterol gallstones: failure to detect a suppression of cholesterol 7α‐hydroxylase activity

Effect of colectomy with ileo‐anal anastomosis on the biliary lipids

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Pretreatment Biliary Lipid Composition in White Patients with Radiol0ucent Gallstones in the National Cooperative Gallstone Study

Cited by 102 publications

References 49 publications

Biliary Cholesterol Hypersecretion in Gallstone–Susceptible Mice Is Associated With Hepatic Up–Regulation of the High–Density Lipoprotein Receptor Srbi

Biliary Cholesterol Hypersecretion in Gallstone–Susceptible Mice Is Associated With Hepatic Up–Regulation of the High–Density Lipoprotein Receptor Srbi

Deoxycholic acid treatment in patients with cholesterol gallstones: failure to detect a suppression of cholesterol 7α‐hydroxylase activity

Effect of colectomy with ileo‐anal anastomosis on the biliary lipids

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Deoxycholic acid treatment in patients with cholesterol gallstones: failure to detect a suppression of cholesterol 7α‐hydroxylase activity