title: N-3 polyunsaturated fatty acid attenuates cholesterol gallstones by suppressing mucin production with a high cholesterol diet in mice.
abstract: OBJECTIVE
  The increasing prevalence of cholesterol gallstone (CG) disease has become an economic burden to the healthcare system. Ursodeoxycholic acid (UDCA) is the only established medical agent used to dissolve gallstones. In investigating novel therapeutics for CG, we assessed the preventive effects of n-3 polyunsaturated fatty acids (n-3PUFA) on the formation of CG induced by feeding a lithogenic diet (LD) containing high cholesterol levels to mice.
  
  
  METHODS
  Mice were divided into the following six groups: (A) regular diet (RD); (B) RD+n-3PUFA; (C) LD; (D) LD+n-3PUFA; (E) LD+UDCA; (F) LD+n-3PUFA+UDCA. After RD/LD feeding for 2 weeks, n-3PUFA or UDCA was administered orally and the diet maintained for 8 weeks. The levels of phospholipids and cholesterol in bile, CG formation, gallbladder wall thickness, MUC gene expression in gallbladder were analyzed.
  
  
  RESULTS
  No stone or sludge was evident in the RD groups (Groups A, B). Mice in the n-3PUFA treatment (Groups D, F) showed significantly lower stone formation than the other LD groups (Groups C, E). The combination treatment of n-3PUFA and UDCA suppressed stone formation more than mono-therapy with n-3PUFA or UDCA. Bile phospholipid levels were significantly elevated in the Group F. Hypertrophy of the gallbladder wall was evident in mice fed LD. MUC 2, 5AC, 5B and 6 mRNA expression levels were significantly elevated in the LD-fed group, and this was suppressed by n-3PUFA with or without UDCA.
  
  
  CONCLUSIONS
  N-3PUFA attenuated gallstone formation in mouse, through increasing the levels of bile phospholipids and suppressing bile mucin formation.
authors: Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors: Ja Kyung
authors: JK
authors: Kim
authors: Soo Min
authors: SM
authors: Cho
authors: So Hee
authors: SH
authors: Kang
authors: Eunjung
authors: E
authors: Kim
authors: Hee
authors: H
authors: Yi
authors: Eun Sun
authors: ES
authors: Yun
authors: Dong Goo
authors: DG
authors: Lee
authors: Hee Jung
authors: HJ
authors: Cho
authors: Yong Han
authors: YH
authors: Paik
authors: Yang Kyu
authors: YK
authors: Choi
authors: Seung Joo
authors: SJ
authors: Haam
authors: Ho Chul
authors: HC
authors: Shin
authors: Dong Ki
authors: DK
authors: Lee
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology / Q000627:therapeutic use; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005704:Gallbladder / Q000473:pathology; D042882:Gallstones / Q000517:prevention & control*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055271:Mucin 5AC / Q000235:genetics; D055262:Mucin-2 / Q000235:genetics; D055257:Mucin-5B / Q000235:genetics; D055272:Mucin-6 / Q000235:genetics; D009077:Mucins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D009092:Mucous Membrane / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002756:Cholagogues and Choleretics; D002791:Cholesterol, Dietary; D015525:Fatty Acids, Omega-3; C524626:Muc2 protein, mouse; D055271:Mucin 5AC; D055262:Mucin-2; D055257:Mucin-5B; D055272:Mucin-6; D009077:Mucins; D010743:Phospholipids; D012333:RNA, Messenger; D014580:Ursodeoxycholic Acid; D002784:Cholesterol