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N-3 polyunsaturated fatty acid attenuates cholesterol gallstones by suppressing mucin production with a high cholesterol diet in mice

 Ja Kyung Kim  ;  Soo Min Cho  ;  So Hee Kang  ;  Eunjung Kim  ;  Hee Yi  ;  Eun Sun Yun  ;  Dong Goo Lee  ;  Hee Jung Cho  ;  Yong Han Paik  ;  Yang Kyu Choi  ;  Seung Joo Haam  ;  Ho Chul Shin  ;  Dong Ki Lee 
 Journal of Gastroenterology and Hepatology, Vol.27(11) : 1745-1751, 2012 
Journal Title
 Journal of Gastroenterology and Hepatology 
Issue Date
Animals ; Bile/metabolism ; Cholagogues and Choleretics/pharmacology ; Cholagogues and Choleretics/therapeutic use ; Cholesterol/metabolism ; Cholesterol, Dietary/pharmacology ; Cholesterol, Dietary/therapeutic use* ; Drug Therapy, Combination ; Fatty Acids, Omega-3/pharmacology ; Fatty Acids, Omega-3/therapeutic use* ; Gallbladder/pathology ; Gallstones/prevention & control* ; Gene Expression/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Mucin 5AC/genetics ; Mucin-2/genetics ; Mucin-5B/genetics ; Mucin-6/genetics ; Mucins/biosynthesis* ; Mucins/drug effects ; Mucins/genetics ; Mucous Membrane/pathology ; Phospholipids/metabolism ; RNA, Messenger/metabolism ; Statistics, Nonparametric ; Ursodeoxycholic Acid/pharmacology ; Ursodeoxycholic Acid/therapeutic use
cholesterol gallstone ; high cholesterol diet ; mucin ; phopholipid ; n-3 polyunsaturated fatty acid
BACKGROUND AND AIM: 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ja Kyung(김자경) ORCID logo https://orcid.org/0000-0001-5025-6846
Paik, Yong Han(백용한)
Lee, Dong Ki(이동기) ORCID logo https://orcid.org/0000-0002-0048-9112
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