title: Association of caveolin-3 and cholecystokinin A receptor with cholesterol gallstone disease in mice.
abstract: OBJECTIVE
  To investigate the role of caveolin-3 (CAV3) and cholecystokinin A receptor (CCKAR) in cholesterol gallstone disease (CGD).
  
  
  METHODS
  To establish a mouse model of CGD, male C57BL/6 mice were fed with a lithogenic diet containing 1.0% cholic acid, 1.25% cholesterol and 15% fat; a similar control group was given a normal diet. The fresh liver weights and liver-to-body weight ratio were compared between the two groups after one month. Serum lipid profile and bile composition were determined with an autoanalyzer. The Cav3 and Cckar mRNA and CAV3 and CCKAR protein levels in the liver and gallbladder were determined via real-time polymerase chain reaction and Western blot, respectively.
  
  
  RESULTS
  Establishment of the mouse CGD model was verified by the presence of cholesterol gallstones in mice fed the lithogenic diet. Compared with mice maintained on a normal diet, those fed the lithogenic diet had significantly higher mean liver-to-body weight ratio (0.067 ± 0.007 vs 0.039 ± 0.007, P < 0.01), serum total cholesterol (4.22 ± 0.46 mmol/L vs 2.21 ± 0.11 mmol/L, P < 0.001), bile total cholesterol (1.33 ± 0.33 mmol/L vs 0.21 ± 0.11 mmol/L, P < 0.001), and bile phospholipid concentrations (3.55 ± 1.40 mmol/L vs 1.55 ± 0.63 mmol/L, P = 0.04), but lower total bile acid concentrations (726.48 ± 51.83 μmol/L vs 839.83 ± 23.74 μmol/L, P = 0.007). The lithogenic diet was also associated with significantly lower CAV3 in the liver and lower CAV3 and CCKAR in the gallbladder compared with the control mice (all P < 0.05).
  
  
  CONCLUSIONS
  CAV3 and CCKAR may be involved in cholesterol gallstone disease.
authors: Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors: Guo-Qiang
authors: GQ
authors: Xu
authors: Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors: Cheng-Fu
authors: CF
authors: Xu
authors: Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors: Hong-Tan
authors: HT
authors: Chen
authors: Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors: Shan
authors: S
authors: Liu
authors: Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors: Xiao-Dong
authors: XD
authors: Teng
authors: Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors: Gen-Yun
authors: GY
authors: Xu
authors: Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors: Chao-Hui
authors: CH
authors: Yu
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002791:Cholesterol, Dietary; D019826:Cholic Acid; D015536:Down-Regulation; D005704:Gallbladder / Q000378:metabolism*; D042882:Gallstones / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043886:Receptor, Cholecystokinin A / Q000235:genetics / Q000378:metabolism*
chemical_list: C495548:Cav3 protein, mouse; D051244:Caveolin 3; C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; D002791:Cholesterol, Dietary; D010743:Phospholipids; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D019826:Cholic Acid
keywords: Caveolin-3; Cholecystokinin A receptor; Cholesterol gallstone disease; Lithogenic diet; Mechanism