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Primary 12 alpha-Hydroxylated Bile Acids Lower Hepatic Iron Concentration in Rats

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Title: Primary 12 alpha-Hydroxylated Bile Acids Lower Hepatic Iron Concentration in Rats
Authors: Hori, Shota Browse this author
Satake, Minako Browse this author
Kohmoto, Ohji Browse this author
Takagi, Ryo Browse this author
Okada, Kazufumi Browse this author
Fukiya, Satoru Browse this author →KAKEN DB
Yokota, Atsushi Browse this author →KAKEN DB
Ishizuka, Satoshi Browse this author →KAKEN DB
Keywords: 12 alpha-hydroxylated bile acid
high-fat diet
iron deficiency
lipocalin 2
primary bile acid
Issue Date: Mar-2021
Publisher: Oxford University Press
Journal Title: Journal of nutrition
Volume: 151
Issue: 3
Start Page: 523
End Page: 530
Publisher DOI: 10.1093/jn/nxaa366
Abstract: Background: Primary 12 alpha-hydroxylated bile acids (12 alpha OH BAs) enhance intestinal iron uptake due to their ability ex vivo to chelate iron. However, no information is available on their role in vivo, especially in the liver. Objectives: To investigate the effects and mechanisms of primary 12 alpha OH BAs on hepatic iron concentration in vivo. Methods: Male Wistar King A Hokkaido male rats (WKAH/HkmSlc) rats aged 4-5 weeks were fed a control diet or a diet with cholic acid (CA; 0.5 g/kg diet), the primary 12 alpha OH BA, for 2 weeks (Study 1) or 13 weeks (Study 2). In Study 3, rats fed the same diets were given drinking water either alone or containing vancomycin (200 mg/L) for 6 weeks. The variables measured included food intake (Studies 1-3), bile acid profiles (Studies 1 and 3), hepatic iron concentration (Studies 1-3), fecal iron excretion (Studies 1 and 2), iron-related liver gene expression (Studies 2 and 3), and plasma iron-related factors (Studies 2 and 3). Results: In Study 1, CA feed reduced the hepatic iron concentration (-16%; P = 0.005) without changing food intake or fecal iron excretion. In Study 2, we found a significant increase in the aortic plasma concentration of lipocalin 2 (LCN2; +65%; P < 0.001), an iron-trafficking protein. In Study 3, we observed no effect of vancomycin treatment on the CA-induced reduction of hepatic iron concentration (-32%; P < 0.001), accompanied by increased plasma LCN2 concentration (+72%; P = 0.003), in the CA-fed rats despite a drastic reduction in the secondary 12 alpha OH BA concentration (-94%; P < 0.001) in the aortic plasma. Conclusions: Primary 12 alpha OH BAs reduced the hepatic iron concentration in rats. LCN2 may be responsible for the hepatic iron-lowering effect of primary 12 alpha OH BAs by transporting iron out of the liver.
Rights: This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Nutrition following peer review. The version of record Shota Hori, Minako Satake, Ohji Kohmoto, Ryo Takagi, Kazufumi Okada, Satoru Fukiya, Atsushi Yokota, Satoshi Ishizuka, Primary 12α-Hydroxylated Bile Acids Lower Hepatic Iron Concentration in Rats, The Journal of Nutrition, Volume 151, Issue 3, March 2021, Pages 523-530, is available online at:
Type: article (author version)
Appears in Collections:農学院・農学研究院 (Graduate School of Agriculture / Faculty of Agriculture) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石塚 敏

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