open access

https://hdl.handle.net/2115/84208

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

英語

primary bile acid

2021-03

Oxford University Press

Journal of nutrition

151(3)

523-530

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.

学術雑誌論文

Accepted Manuscript

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: https://doi.org/10.1093/jn/nxaa366

0022-3166