Ezetimibe ameliorates cholecystosteatosis.
BACKGROUND
Cholecystosteatosis is the accumulation of gallbladder wall fats leading to decreased gallbladder emptying. Ezetimibe inhibits intestinal fat absorption and prevents murine gallstone formation. However, the influence of ezetimibe on gallbladder emptying and cholecystosteatosis has not been studied. Therefore, we tested the hypothesis that ezetimibe would improve gallbladder motility by preventing the buildup of fats in the gallbladder wall.


METHODS
Forty lean female mice were fed either a control diet or a lithogenic diet for 6 weeks. Half of the mice on each diet received ezetimibe. At 11 weeks of age, all mice were fasted overnight and underwent gallbladder ultrasonography to determine ejection fraction. One week later, the mice were fasted and underwent cholecystectomy. Bile was examined for cholesterol crystals. The gallbladders were snap-frozen for lipid analysis.


RESULTS
The lithogenic diet significantly (P < 0.05) increased serum cholesterol, biliary crystals, gallbladder wall cholesterol and cholesterol/phospholipid ratio, and decreased gallbladder ejection fraction. All of these abnormalities were reversed (P < 0.05) by the addition of ezetimibe to the diet.


CONCLUSIONS
These data suggest that ezetimibe lowers serum cholesterol, prevents biliary crystals, and normalizes gallbladder wall fat and function. We conclude that ezetimibe ameliorates cholecystosteatosis and may be an effective agent for gallstone prevention.
Mathur
Abhishek
A
Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind, USA.
Walker
Julia J
JJ
Al-Azzawi
Hayder H
HH
Lu
Debao
D
Swartz-Basile
Deborah A
DA
Nakeeb
Attila
A
Pitt
Henry A
HA
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood / Q000737:chemistry; D002788:Cholesterol Esters / Q000378:metabolism; D003460:Crystallization; D004041:Dietary Fats / Q000378:metabolism*; D000069438:Ezetimibe; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism; D005705:Gallbladder Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000097:blood / Q000737:chemistry; D014280:Triglycerides / Q000097:blood / Q000737:chemistry; D014463:Ultrasonography
D000924:Anticholesteremic Agents; D001384:Azetidines; D002788:Cholesterol Esters; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol; D000069438:Ezetimibe