Lack of endogenous cholecystokinin promotes cholelithogenesis in mice

H. H. Wang, M. Liu, P. Portincasa, P. Tso, David Q.H. Wang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Cholecystokinin (CCK) release from the proximal small intestine and gallbladder emptying in response to a fatty meal are greatly reduced in celiac patients before they start the gluten-free diet, showing a genetic predisposition to gallstones. Methods: To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous CCK on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days. Key Results: Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high-fat diet was impaired in CCK knockout (KO) mice compared to wild-type mice. Because of the absence of CCK, small intestinal transit time was prolonged and intestinal cholesterol absorption was increased. During 28 days of feeding, elevated biliary cholesterol concentrations and gallbladder stasis promoted the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. Thus, cholesterol crystallization and gallstone formation were accelerated in CCK KO mice. In contrast, daily intraperitoneal administration of CCK-8 reduced gallstone formation in CCK KO mice even on the lithogenic diet. Conclusions & Inferences: The lack of endogenous CCK enhances susceptibility to gallstones by impairing gallbladder contractile function and small intestinal motility function. These findings show that celiac disease is an important risk factor for gallstone formation and the gallbladder motility function should be routinely examined by ultrasonography and gallbladder stasis should be prevented in celiac patients.

Original languageEnglish (US)
Pages (from-to)364-375
Number of pages12
JournalNeurogastroenterology and Motility
Volume28
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Cholecystokinin
Gallstones
Gallbladder
Celiac Disease
Gallbladder Emptying
Cholesterol
Knockout Mice
Crystallization
Abdomen
Diet
Gluten-Free Diet
Gastrointestinal Motility
Glutens
Intestinal Absorption
High Fat Diet
Genetic Predisposition to Disease
Hypercholesterolemia
Small Intestine
Meals
Fasting

Keywords

  • Bile salt
  • Celiac disease
  • Cholesterol absorption
  • Cholesterol crystallization
  • Gallbladder motility
  • Lithogenic bile

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

Lack of endogenous cholecystokinin promotes cholelithogenesis in mice. / Wang, H. H.; Liu, M.; Portincasa, P.; Tso, P.; Wang, David Q.H.

In: Neurogastroenterology and Motility, Vol. 28, No. 3, 01.03.2016, p. 364-375.

Research output: Contribution to journalArticle

Wang, H. H. ; Liu, M. ; Portincasa, P. ; Tso, P. ; Wang, David Q.H. / Lack of endogenous cholecystokinin promotes cholelithogenesis in mice. In: Neurogastroenterology and Motility. 2016 ; Vol. 28, No. 3. pp. 364-375.
@article{2178b5f89cc349ecada2b665886066b3,
title = "Lack of endogenous cholecystokinin promotes cholelithogenesis in mice",
abstract = "Background: Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Cholecystokinin (CCK) release from the proximal small intestine and gallbladder emptying in response to a fatty meal are greatly reduced in celiac patients before they start the gluten-free diet, showing a genetic predisposition to gallstones. Methods: To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous CCK on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days. Key Results: Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high-fat diet was impaired in CCK knockout (KO) mice compared to wild-type mice. Because of the absence of CCK, small intestinal transit time was prolonged and intestinal cholesterol absorption was increased. During 28 days of feeding, elevated biliary cholesterol concentrations and gallbladder stasis promoted the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. Thus, cholesterol crystallization and gallstone formation were accelerated in CCK KO mice. In contrast, daily intraperitoneal administration of CCK-8 reduced gallstone formation in CCK KO mice even on the lithogenic diet. Conclusions & Inferences: The lack of endogenous CCK enhances susceptibility to gallstones by impairing gallbladder contractile function and small intestinal motility function. These findings show that celiac disease is an important risk factor for gallstone formation and the gallbladder motility function should be routinely examined by ultrasonography and gallbladder stasis should be prevented in celiac patients.",
keywords = "Bile salt, Celiac disease, Cholesterol absorption, Cholesterol crystallization, Gallbladder motility, Lithogenic bile",
author = "Wang, {H. H.} and M. Liu and P. Portincasa and P. Tso and Wang, {David Q.H.}",
year = "2016",
month = "3",
day = "1",
doi = "10.1111/nmo.12734",
language = "English (US)",
volume = "28",
pages = "364--375",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Lack of endogenous cholecystokinin promotes cholelithogenesis in mice

AU - Wang, H. H.

AU - Liu, M.

AU - Portincasa, P.

AU - Tso, P.

AU - Wang, David Q.H.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background: Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Cholecystokinin (CCK) release from the proximal small intestine and gallbladder emptying in response to a fatty meal are greatly reduced in celiac patients before they start the gluten-free diet, showing a genetic predisposition to gallstones. Methods: To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous CCK on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days. Key Results: Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high-fat diet was impaired in CCK knockout (KO) mice compared to wild-type mice. Because of the absence of CCK, small intestinal transit time was prolonged and intestinal cholesterol absorption was increased. During 28 days of feeding, elevated biliary cholesterol concentrations and gallbladder stasis promoted the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. Thus, cholesterol crystallization and gallstone formation were accelerated in CCK KO mice. In contrast, daily intraperitoneal administration of CCK-8 reduced gallstone formation in CCK KO mice even on the lithogenic diet. Conclusions & Inferences: The lack of endogenous CCK enhances susceptibility to gallstones by impairing gallbladder contractile function and small intestinal motility function. These findings show that celiac disease is an important risk factor for gallstone formation and the gallbladder motility function should be routinely examined by ultrasonography and gallbladder stasis should be prevented in celiac patients.

AB - Background: Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Cholecystokinin (CCK) release from the proximal small intestine and gallbladder emptying in response to a fatty meal are greatly reduced in celiac patients before they start the gluten-free diet, showing a genetic predisposition to gallstones. Methods: To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous CCK on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days. Key Results: Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high-fat diet was impaired in CCK knockout (KO) mice compared to wild-type mice. Because of the absence of CCK, small intestinal transit time was prolonged and intestinal cholesterol absorption was increased. During 28 days of feeding, elevated biliary cholesterol concentrations and gallbladder stasis promoted the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. Thus, cholesterol crystallization and gallstone formation were accelerated in CCK KO mice. In contrast, daily intraperitoneal administration of CCK-8 reduced gallstone formation in CCK KO mice even on the lithogenic diet. Conclusions & Inferences: The lack of endogenous CCK enhances susceptibility to gallstones by impairing gallbladder contractile function and small intestinal motility function. These findings show that celiac disease is an important risk factor for gallstone formation and the gallbladder motility function should be routinely examined by ultrasonography and gallbladder stasis should be prevented in celiac patients.

KW - Bile salt

KW - Celiac disease

KW - Cholesterol absorption

KW - Cholesterol crystallization

KW - Gallbladder motility

KW - Lithogenic bile

UR - http://www.scopus.com/inward/record.url?scp=84958544290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958544290&partnerID=8YFLogxK

U2 - 10.1111/nmo.12734

DO - 10.1111/nmo.12734

M3 - Article

C2 - 26604077

AN - SCOPUS:84958544290

VL - 28

SP - 364

EP - 375

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

IS - 3

ER -