Lack of adiponectin promotes formation of cholesterol gallstones in mice.
Plasma adiponectin levels are reduced in obese people, and hypoadiponectinemia is recently reported to associate with cholesterol gallstone formation in human. The aim of this study was to examine the role of adiponectin in gallstone formation using adiponectin knockout mice. We analyzed male knockout and C57BL6J mice fed normal or lithogenic diet for 6 weeks. On lithogenic diet, the prevalence rate of gallstone was significantly greater in knockout mice than C57BL6J mice. The molar percentages of beta and omega-muricholic acid were significantly higher and hepatic sterol 12 alpha-hydroxylase expression (cyp8b1) was significantly lower in knockout mice than C57BL6J mice fed normal diet. The bile apolipoprotein A-I protein levels were decreased in knockout mice. Histological examination showed gallbladder wall thickening and accumulation of glycoprotein in the gallbladder of knockout mice. Gallbladder phospholipase A2-IVA expression was significantly higher in knockout mice than in C57BL6J mice fed lithogenic diet. Our results indicate that lack of adiponectin promotes gallstone formation in mice.
Ogiyama
Hideharu
H
Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Kamada
Yoshihiro
Y
Kiso
Shinichi
S
Araki
Hiroshi
H
Yamada
Takuya
T
Nishihara
Tamao
T
Watabe
Kenji
K
Tochino
Yoshihiro
Y
Kihara
Shinji
S
Funahashi
Tohru
T
Kanno
Keishi
K
Shimomura
Iichiro
I
Tsutsui
Shusaku
S
Tazuma
Susumu
S
Hayashi
Norio
N
D052242:Adiponectin / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D005704:Gallbladder / Q000201:enzymology / Q000473:pathology; D042882:Gallstones / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013253:Steroid 12-alpha-Hydroxylase / Q000235:genetics
D052242:Adiponectin; D016632:Apolipoprotein A-I; D002784:Cholesterol; D013253:Steroid 12-alpha-Hydroxylase; D054513:Group IV Phospholipases A2