Division of Fundamental Agriscience Research, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan.
J Nutr. 2021 Mar 11;151(3):523-530. doi: 10.1093/jn/nxaa366.
Primary 12α-hydroxylated bile acids (12αOH 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.
To investigate the effects and mechanisms of primary 12αOH BAs on hepatic iron concentration in vivo.
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 12αOH 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).
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 12αOH BA concentration (-94%; P < 0.001) in the aortic plasma.
Primary 12αOH BAs reduced the hepatic iron concentration in rats. LCN2 may be responsible for the hepatic iron-lowering effect of primary 12αOH BAs by transporting iron out of the liver.
初级 12α-羟化胆酸（12αOH BAs）能够螯合铁，因此能够增强肠道铁的摄取，但其在体内的作用尚不清楚，尤其是在肝脏中的作用。
研究初级 12αOH BAs 对体内肝脏铁浓度的影响及其机制。
4-5 周龄雄性 Wistar King A Hokkaido 雄性大鼠（WKAH/HkmSlc）喂食对照饮食或含胆酸（CA；0.5 g/kg 饮食）的饮食 2 周（研究 1）或 13 周（研究 2）。在研究 3 中，喂食相同饮食的大鼠给予饮用水或含有万古霉素（200 mg/L）的饮用水 6 周。测量的变量包括食物摄入量（研究 1-3）、胆汁酸谱（研究 1 和 3）、肝脏铁浓度（研究 1-3）、粪便铁排泄量（研究 1 和 2）、与铁相关的肝脏基因表达（研究 2 和 3）和血浆与铁相关的因子（研究 2 和 3）。
在研究 1 中，CA 喂养降低了肝脏铁浓度（-16%；P=0.005），而不改变食物摄入量或粪便铁排泄量。在研究 2 中，我们发现主动脉血浆中脂联素 2（LCN2；+65%；P<0.001）的浓度显著升高，这是一种铁转运蛋白。在研究 3 中，我们观察到万古霉素治疗对 CA 诱导的肝脏铁浓度降低（-32%；P<0.001）没有影响，尽管 CA 喂养大鼠的次级 12αOH BA 浓度急剧降低（-94%；P<0.001），但主动脉血浆中的 LCN2 浓度仍升高（+72%；P=0.003）。
初级 12αOH BAs 降低了大鼠肝脏铁浓度。LCN2 可能通过将铁从肝脏中转运出来，从而介导初级 12αOH BAs 的降低肝脏铁浓度作用。
