Studies On The Antagonistic Mechanism Of Metabolic Pathways Mediated By Transferrin1 And Ferritin In Dietary Iron Absorption

Iron is an essential trace element of human body and plays a complex and irreplaceable role in maintaining life activities.However,iron deficiency is the top three"invisible hungers" in the world,with about a fifth of the world's population suffering from iron deficiency anemia.Compared with the western developed countries,China's iron shortage is particularly serious,affecting a wide area,involving a large number of people.Irrational dietary structure and lack of knowledge of iron nutrition are the main causes of iron malnutrition among Chinese residents.With the improvement of people's living standards,nutrition,safety and health have become the theme of food development.The research on functional components of food and the development of functional trace element supplementary food have become the focus of food research at home and abroad.The development of functional food needs basic scientific research to provide theoretical support and basis for it,but the mechanism of iron metabolism has not been fully clarified.For example,there are many ways of iron absorption in mammals,some tissues need iron supplementation mediated by transferrin(Tsf),and some need iron supplementation mediated by Ferritin.While,the relationship of different iron absorption pathways are still unclear.Therefore,it is of scientific significance and application value to study the absorption,transport,recycling and storage of iron ions in vivo for better regulation of iron homeostasis,prevention of diseases related to iron metabolism disorders,development of functional food and guiding people to have a reasonable diet.As a classical model organism,Drosophila melanogaster has been widely used in food nutrition and health in recent years because of its clear genetic background,convenient gene regulation and short growth cycle.In this study,we investigate the function of Drosophila melanogaster Tsfl in iron metabolism and the relationship between the two iron absorption pathways mediated by Tsfl and Ferritin respectively.The main research contents and results are as follows:(1)Abundance of Tsfl in different tissues of Drosophila melanogaster.The results showed that Tsfl was a widely expressed protein in the larvae of Drosophila melanogaster,and fat body(similar to mammalian liver)and trachea were the main expression sites.(2)Tsfl is involved in iron metabolism of Drosophila melanogaster.In this study,we confirmed that Tsfl participates in iron metabolism in Drosophila melanogaster from two aspects:on the one hand,we found that high-iron diet can inhibit the expression of Tsfl,low-iron diet can induce it;On the other hand,Tsf1 knockdown flies in the whole body are sensitive to iron-depleted food and Tsf1 overexpression flies are sensitive to iron-repleted food.From these two aspects,we basically determined that Tsfl was involved in iron metabolism in(3)Tsfl synthesized by fat body participates in transferring iron from the midgut to the fat body.Through a variety of experimental methods,it was found that silencing Tsfl in fat body led to iron accumulation in the midgut and iron deficiency in the fat body.Based on the experimental results,we infer that the Tsfl synthesized by the fat body is involved in transporting iron absorbed by the intestine into the fat body.(4)Tsfl competes with dZIP13/Ferritin for iron in the midgut.The midgut specific knock down of Tsf1 rescued the developmental defects caused by dZIP13/Ferritin knocking down.Subsequent experiments found that this kind of rescue was achieved by increasing iron content in whole body.Prussian blue staining showed that Tsfl knockdown restored iron reduction in the secretory pathway caused by dZIP13/Ferritin knockdown.According to the experimental results,we speculate that Tsfl synthesized by midgut can compete with dZIP13/Ferritin for iron.In conclusion,on the one hand,this study identified the function of Tsf1 in Drosophila melanogaster,indicating that iron metabolism is conserved among species.Drosophila melanogaster can be used as a good model for future iron nutrition research.On the other hand,the competitive relationship between the two iron uptake pathways mediated by Tsfl and Ferritin was discussed.These findings expand and improve our understanding of iron metabolism,and provide important clues and theoretical basis for the future development of functional food and the treatment of iron metabolism disorders related diseases.