Gallstone Formation Follows a Different Trajectory in Bariatric Patients Compared to Nonbariatric Patients

Since obese patients form cholesterol gallstones very rapidly after bariatric surgery, in patients who did not form gallstones during preceding years, we hypothesized that gallstone formation follows a different trajectory in bariatric patients compared to nonbariatric patients. We therefore analyzed the lipid composition of gallbladder bile derived from 18 bariatric gallstone patients and 17 nonbariatric gallstone patients (median (IQR) age, 46.0 (28.0–54.0) years; 33 (94%) female) during laparoscopic cholecystectomy using an enzymatic and lipidomics approach. We observed a higher concentration of total lipids (9.9 vs. 5.8 g/dL), bile acids (157.7 vs. 81.5 mM), cholesterol (10.6 vs. 5.4 mM), and phospholipids (30.4 vs. 21.8 mM) in bariatric gallstone patients compared to nonbariatric gallstone patients. The cholesterol saturation index did not significantly differ between the two groups. Lipidomics analysis revealed an interesting pattern. Enhanced amounts of a number of lipid species were found in the gallbladder bile of nonbariatric gallstone patients. Most striking was a fivefold higher amount of triglyceride. A concomitant ninefold increase of apolipoprotein B was found, suggesting secretion of triglyceride-rich lipoproteins (TRLs) at the canalicular pole of the hepatocyte in livers from nonbariatric gallstone patients. These findings suggest that gallstone formation follows a different trajectory in bariatric patients compared to nonbariatric patients. Impaired gallbladder emptying might explain the rapid gallstone formation after bariatric surgery, while biliary TRL secretion might contribute to gallstone formation in nonbariatric patients.

Protective Effects of Yinchenhao Decoction on Cholesterol Gallstone in Mice Fed a Lithogenic Diet by Regulating LXR, CYP7A1, CYP7B1, and HMGCR Pathways

The study attempted to elucidate whether lipid genes are closely associated with lipid metabolic abnormalities during the lithogenic time and how Yinchenhao Decoction (YCHD) works on the transcriptions of lipid genes against cholesterol gallstone model. C57BL/6J mice fed on lithogenic diet (LD) were used for model establishment and randomized into 5 groups. All groups received LD for different weeks with isometrically intragastric administration of YCHD or NS. Biochemical tests were measured and liver tissues were harvested for histological and genetic detection. It was found that all groups with increasing LD showed a following tendency of gallstone incidence, bile cholesterol, phospholipids, total bile acid, and cholesterol saturation index (CSI). Conversely, YCHD could significantly normalize the levels of gallstone incidence, bile lipids, and CSI (CSI<1). As lithogenic time progressed, ABCG5, ABCG8, PPAR-α, and ABCB4 were upregulated, and SREBP2, CYP7A1, and CYP7B1 were downregulated, while CYP7A1, CYP7B1, LXR, and HMGCR mRNA were increased 3-fold under the administration of YCHD. It was concluded that abnormal expressions of the mentioned genes may eventually progress to cholesterol gallstone. CYP7A1, CYP7B1, LXR, and HMGCR mRNA may be efficient targets of YCHD, which may be a preventive drug to reverse liver injury, normalize bile lipids, facilitate gallstone dissolution, and attenuate gallstone formation.

Anti-cholelithogenic effect of dietary tender cluster beans (Cyamopsis tetragonoloba) on the formation of cholesterol gallstones in mice

Providing a lithogenic diet that contains 0.5% cholesterol to experimental mice for 10 weeks resulted in cholesterol supersaturation in gallbladder bile, which induced the formation of cholesterol gallstones. In this study, to evaluate the anti-cholelithogenic potential of dietary tender cluster bean, a freeze-dried powder of the test legume was included in the lithogenic diet at 5%, 10%, and 15%. Dietary cluster beans reduced the cholesterol gallstone incidence by 43%, 46%, and 58% at the respective doses. Dietary cluster beans markedly reduced biliary cholesterol and, hence, the cholesterol saturation index. This was corroborated by the beneficial modification of the cholesterol/phospholipid ratio and the cholesterol/bile acid ratio in the bile. Dietary cluster beans countered the alterations in serum and liver cholesterol and lipid profiles caused by the lithogenic diet. Thus, dietary tender cluster beans exerted an anti-cholelithogenic influence by decreasing cholesterol hypersecretion into bile and, hence, the cholesterol saturation index, decreasing the formation of lithogenic bile in experimental mice.

Fenugreek seeds reduce atherogenic diet-induced cholesterol gallstone formation in experimental mice

Dietary hypocholesterolemic adjuncts may have a beneficial role in the prevention and treatment of cholesterol gallstones (CGS). In this investigation, fenugreek (Trigonella foenum-graecum) seed was evaluated for this potential on the experimental induction of CGS in laboratory mice. CGS was induced by maintaining mice on a lithogenic diet (0.5% cholesterol) for 10 weeks. Fenugreek seed powder was included at 5%, 10%, and 15% of this lithogenic diet. Dietary fenugreek significantly lowered the incidence of CGS in these mice; the incidence was 63%, 40%, and 10% in the 5%, 10%, and 15% fenugreek groups, respectively, compared with 100% in the lithogenic control. The antilithogenic influence of fenugreek is attributable to its hypocholesterolemic effect. Serum cholesterol level was decreased by 26%–31% by dietary fenugreek, while hepatic cholesterol was lowered by 47%–64% in these high cholesterol-fed animals. Biliary cholesterol was 8.73–11.2 mmol/L as a result of dietary fenugreek, compared with 33.6 mmol/L in high-cholesterol feeding without fenugreek. Cholesterol saturation index in bile was reduced to 0.77–0.99 in fenugreek treatments compared with 2.57 in the high-cholesterol group. Thus, fenugreek seed offers health-beneficial antilithogenic potential by virtue of its favourable influence on cholesterol metabolism.

Stability of Human Gallbladder Bile: Effect of Freezing

In the present study, the stability of the most essential biliary parameters of human gallbladder bile at -18°C was examined over several months. In 12 patients with gallstone disease (10 female, two male; 52.1±13.3 years of age), bile was obtained through fine needle puncture of the gallbladder under local anesthetic. The concentrations of total lipids, cholesterol, phospholipids and bile acids, and the cholesterol saturation index and crystal appearance time were determined before and after freezing over a mean period of 4.38±2.9 months. Gallbladder bile obtained by fine needle puncture has proved to be of excellent quality. The total lipid concentration was unchanged before (8.30±4.16 g/dL) and after freezing (9.16±4.54 g/dL, P=0.6027). The biliary cholesterol, phospholipids and bile acid concentrations, and cholesterol saturation index showed no statistically significant differences before and after freezing. A significant difference arises in the context of subdivision of the group to the nucleation time. Before freezing, most patients had a nucleation time between five and eight days, which shortened to between one and four days after thawing (P=0.0100). The authors conclude that, with the exception of the nucleation time, human gallbladder bile can be stored at -18°C for four months with stability of major lipid components.

Effect of endoscopic sphincterotomy on gall bladder bile lithogenicity and motility

Background—Endoscopic sphincterotomy has been shown to inhibit stone formation in the gall bladder of experimental animals.Aims—To investigate the alterations in bile composition and gall bladder motility after endoscopic sphincterotomy.Patients—A study was performed of gall bladder bile composition and gall bladder motility in patients with gallstone disease ((n = 20; age 40–60 years, median age 55 years: seven men), with gall bladder calculi (n = 12) and with diseased gall bladder (chronic inflammation) without gall bladder calculi (n = 8)), who had received endoscopic sphincterotomy for common bile duct stones. Age and sex matched disease controls comprised 20 patients with gallstone disease but without stones and an intact sphincter of Oddi (with gall bladder calculi (n = 10) and diseased gall bladder without gall bladder calculi (n = 10)).Methods—Gall bladder motility was assessed by ultrasound. Duodenal bile collected by nasoduodenal tube after stimulation of gall bladder by intravenous ceruletid infusion was analysed for cholesterol, phospholipid, and bile acid concentrations, cholesterol saturation index, and nucleation time.Results—There was a significant reduction in mean (SEM) fasting volume (12.5 (1.7) ml v 26.4 (2.5) ml; p<0.001) and mean (SEM) residual volume (4.34 (0.9) ml v14.7 (0.98) ml; p<0.001), and increase in mean (SEM) ejection fraction (65.7 (4.2)% v 43.6 (5.52)%; p<0.001) and mean (SEM) rate constant of gall bladder emptying (−0.031/min v−0.020/min; p<0.01) in patients who had been subjected to endoscopic sphincterotomy. Median nucleation time was significantly longer (17 days v 6 days; p<0.006) in treated patients. There was a reduction in total mean (SEM) lipid concentrations (6.73 (0.32) g/dlv 7.72 (0.84) g/dl; p<0.05), cholesterol (5.6 (1.5) mmol/l v 10.3 (2.23) mmol/l; p<0.001) and CSI (0.72 (0.15) v 1.32 (0.31); p<0.001). There was no significant change in mean (SEM) phospholipid (25.6 (3.5) mmol/l v23.4 (6.28) mmol/l) and bile acid (93.7 (7.31) mmol/l v105.07 (16.6) mmol/l) concentrations.Conclusions—After endoscopic sphincterotomy there was enhanced contractility of the gall bladder, accompanied by a prolongation of nucleation time and reduction in cholesterol saturation index.