High dietary iron reduces transporters involved in iron and manganese metabolism and increases intestinal permeability in calves
High dietary iron reduces transporters involved in iron and manganese metabolism and increases intestinal permeability in calves
复制标题
DOI：
10.3168/jds.2009-2341
复制
发表时间：
2010-02-01
影响因子：
3.5
通讯作者：
Spears, J. W.
中科院分区：
文献类型：
--
作者：
Hansen, S. L.;Ashwell, M. S.;Spears, J. W.
本研究采用56 d的试验设计，研究了高铁日粮对铁锰代谢相关金属转运蛋白的影响。将14头断奶荷斯坦犊牛按体重分层，随机分为2组：1）不补铁（正常铁）或2）补铁750 mg/kg（高铁）。在第0、35和56天采集颈静脉血。在试验结束时，人道处死每个处理组的6头小牛，并采集十二指肠刮片、肝脏和心脏进行分析。另外，将十二指肠近端安装在Ussing室上以评估肠屏障完整性。小牛接受高饮食铁显示跨上皮电阻降低和放射性标记的甘露醇的顶部到基底侧流量增加，表明高铁增加肠道通透性。饲喂高铁日粮降低了犊牛的平均日增重、干物质采食量，和饲料效率。血红蛋白和血清铁浓度没有不同，由于饮食治疗。高膳食铁增加铁在肝脏中的浓度，但不影响心脏或十二指肠铁浓度。十二指肠锰浓度降低喂养高铁饮食，但肝脏和心脏锰浓度不受影响。如通过实时逆转录PCR所确定的，在饲喂高膳食铁的小牛中，编码铁调节激素铁调素的基因的相对肝脏表达是5倍。铁调素响应于增加的铁状态而释放，并与铁输出蛋白膜铁转运蛋白结合，导致膜铁转运蛋白降解，从而减少膳食铁吸收。通过十二指肠蛋白质的Western印迹证实了这一结果，这表明在饲喂高膳食铁的小牛中膜铁转运蛋白减少。十二指肠蛋白表达的二价金属转运蛋白1（DMT 1），铁进口蛋白，也可以运输锰，往往减少高膳食铁。处理后，肝脏和十二指肠中参与铁代谢的几个基因的转录水平没有变化。总之，饲喂犊牛高铁饮食诱导了一种信号级联（铁调素），旨在减少铁的吸收（通过减少膜铁转运蛋白和DMT 1的蛋白表达），其方式与啮齿动物中报道的相似。此外，DAM蛋白水平的降低似乎会降低十二指肠锰，这表明锰也可能是牛中DMT 1的底物。
A 56-d experiment was designed to examine the effect of high dietary Fe on metal transporters involved in Fe and Mn metabolism. Fourteen weaned Holstein calves were stratified by weight and randomly assigned to I of 2 treatments: 1) no supplemental Fe (normal Fe) or 2) 750 mg of supplemental Fe/kg of dry matter (high Fe). Jugular blood was collected on d 0, 35, and 56. At the end of the trial, 6 calves per treatment were humanely killed and duodenal scrapings, liver, and heart were collected for analysis. Additionally., proximal duodenum was mounted on Ussing chambers to assess intestinal barrier integrity. Calves receiving high dietary Fe displayed decreased transepithelial resistance and increased apical-to-basolateral flux of radiolabeled mannitol, suggesting that high Fe created increased intestinal permeability. Feeding calves a diet high in Fe decreased average daily gain, dry matter intake., and feed efficiency. Hemoglobin and serum Fe concentrations did not differ due to dietary treatment. High dietary Fe increased concentrations of Fe in the liver, but did not affect heart or duodenal Fe concentrations. Duodenal Mn concentrations were lowered by feeding a high Fe diet, but liver and heart Mn concentrations were not affected. As determined by real-time reverse transcription PCR, relative hepatic expression of the gene that encodes the Fe regulatory hormone hepcidin was 5-fold greater in calves fed high dietary Fe. Hepcidin is released in response to increased Fe status and binds to the Fe export protein ferroportin causing ferroportin to be degraded, thereby reducing dietary Fe absorption. Confirmation of this result was achieved through Western blotting of duodenal protein, which revealed that ferroportin was decreased in calves fed high dietary Fe. Duodenal protein expression of divalent metal transporter 1 (DMT1), a Fe import protein that can also transport Mn, tended to be reduced by high dietary Fe. Transcript levels of several genes involved in Fe metabolism in liver and duodenum were unchanged by treatment. In summary, feeding calves a diet high in Fe induced a signal cascade (hepcidin) designed to reduce absorption of Fe (via reduced protein expression of ferroportin and DMT1) in a manner similar to that reported in rodents. Additionally, reduced levels of DAM protein appeared to decrease duodenal Mn, suggesting that Mn may also be a substrate for DMT1 in cattle.