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Cholecystokinin (<jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>) 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\u2010free diet, showing a genetic predisposition to gallstones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high\u2010fat diet was impaired in <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> knockout (<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice compared to wild\u2010type mice. Because of the absence of <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>, 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 <jats:styled-content style=\"fixed-case\">CCK KO<\/jats:styled-content> mice. In contrast, daily intraperitoneal administration of <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>\u20108 reduced gallstone formation in <jats:styled-content style=\"fixed-case\">CCK KO<\/jats:styled-content> mice even on the lithogenic diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>The lack of endogenous <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12734","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T07:21:46Z","timestamp":1448436106000},"page":"364-375","source":"Crossref","is-referenced-by-count":17,"title":["Lack of endogenous cholecystokinin promotes cholelithogenesis in mice"],"prefix":"10.1111","volume":"28","author":[{"given":"H. 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