Hepatic gene expression profile of rats fed an iron-deficient diet

Iron is an essential nutritional element; its deficiency in the body causes nutritional problems and a decrease in iron storage that can lead to anemia. The liver not only stores iron but is an important metabolic target as well. Dietary iron deficiency is associated with changes in the metabolism of nutrients such as lipids. However, to the best of our knowledge, a global analysis detailing the consequences of iron deficiency in the body has not yet been reported. We performed a comprehensive transcriptome analysis using DNA microarray technology to reveal the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet or a control diet for 16 days. On day 17, the rats were sacrificed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 up-regulated and 500 down-regulated probe sets to characterize the iron-deficient diet group. The up-regulated probe sets contained genes for enzymes that are involved in cholesterol, amino acid, and glucose metabolisms, as well as in apoptosis. The down-regulated probe sets included genes for enzymes associated with lipid metabolism. Additionally, the 16-day iron-deficient diet induced anemia. Our gene expression analysis revealed that, as a result, cholesterol biosynthesis, gluconeogenesis, and apoptosis due to endoplasmic reticulum stress were accelerated, while fatty acid biosynthesis was suppressed by dietary iron deficiency. Our analysis also showed that cholesterol metabolism, including bile acid biosynthesis, was accelerated in the initial stages of cholesterol accumulation.铁是人体必需的营养元素；体内铁缺乏会引发营养代谢异常，且铁储备减少可导致贫血。肝脏不仅是铁的储存器官，同时也是重要的代谢靶器官。膳食铁缺乏与脂质等营养物质的代谢改变密切相关。然而，据我们所知，目前尚未有研究对体内铁缺乏所产生的影响开展全面系统性分析。本研究采用DNA微阵列（DNA microarray）技术开展全面转录组分析，以揭示铁缺乏对肝脏基因表达的调控作用。将4周龄大鼠分为两组，分别饲喂缺铁日粮与对照日粮，持续16天。第17天时，对大鼠实施麻醉并处死，摘取肝脏用于DNA微阵列分析。本研究共鉴定得到600个上调探针集与500个下调探针集，以此表征缺铁日粮组的基因表达特征。上调探针集所包含的基因涵盖了参与胆固醇、氨基酸、葡萄糖代谢及细胞凋亡过程的酶编码基因；下调探针集则包含了与脂质代谢相关的酶编码基因。此外，为期16天的缺铁日粮饲喂成功诱导了贫血症状。本研究的基因表达分析结果显示，膳食铁缺乏可促进胆固醇生物合成、糖异生过程以及内质网应激介导的细胞凋亡，同时抑制脂肪酸生物合成。此外，本研究还发现，在胆固醇蓄积的初始阶段，包括胆汁酸生物合成在内的胆固醇代谢过程均被加速激活。