Role of Slc19a1 and Tfr2 in liver transport of iron and folate: A rat model of folate/iron deficiency followed by supplementation

J Trace Elem Med Biol. 2020 Dec:62:126568. doi: 10.1016/j.jtemb.2020.126568. Epub 2020 Jun 1.

Abstract

The aim of this study was to determine how folate and iron deficiency, and the subsequent supplementation of rats' diet with these nutrients, affects Slc19a1and Tfr2 gene expression and the metabolism of folate and iron. After 28 days of iron-folate deficiency 150 female rats were randomized into five experimental groups receiving a diet deficient in folic acid (FA), an iron-supplemented diet (DFE), an iron-deficient diet supplemented with FA (DFOL), a diet supplemented with iron and FA (FEFOL), and a diet deficient in iron and FA (D); there was also a control group (C). Samples were collected on days 2, 10, and 21 of the experiment. After two days of supplementation, Tfr2 mRNA level were 78 % lower in the DFE group than in the C group (p < 0.05); after 10 days, TfR2 levels in the FEFOL group were 82 % lower than in the C and the DFE group (p < 0.01). However, we did not find any differences at the protein level at any time-point. Hepcidin concentrations were higher in the DFE and the DFEFOL groups than in the D group after 21 days of supplementation (p < 0.01). Transcript and protein abundance of Slc19a1 gene did not differ between the groups at any time-point. Iron metabolism was affected by iron and folate deficiency and subsequent supplementation with these micronutrients, but TFR2 protein was not involved in the regulatory mechanism. Hepcidin expression can be are upregulated after 21 days of supplementation with 150 mg of iron/ kg of diet.

Keywords: Folate; Iron; Liver; Supplementation; Transporters.

MeSH terms

  • Animals
  • Biological Transport
  • Dietary Supplements
  • Disease Models, Animal
  • Female
  • Folic Acid / metabolism
  • Folic Acid / pharmacology
  • Folic Acid Deficiency / diet therapy
  • Folic Acid Deficiency / metabolism*
  • Gene Expression Regulation / drug effects
  • Hepcidins / metabolism
  • Iron / metabolism
  • Iron / pharmacology
  • Iron Deficiencies*
  • Liver / drug effects
  • Liver / metabolism*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • Rats, Wistar
  • Receptors, Transferrin / genetics
  • Receptors, Transferrin / metabolism*
  • Reduced Folate Carrier Protein / genetics
  • Reduced Folate Carrier Protein / metabolism*

Substances

  • Hepcidins
  • Membrane Transport Proteins
  • Minor Histocompatibility Antigens
  • Receptors, Transferrin
  • Reduced Folate Carrier Protein
  • Slc19a1 protein, rat
  • Tfr2 protein, rat
  • Folic Acid
  • Iron