title: Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis.
abstract: Vitamin A modulates inflammatory status, iron metabolism and erythropoiesis. Given that these factors modulate the expression of the hormone hepcidin (Hamp), we investigated the effect of vitamin A deficiency on molecular biomarkers of iron metabolism, the inflammatory response and the erythropoietic system. Five groups of male Wistar rats were treated: control (AIN-93G), the vitamin A-deficient (VAD) diet, the iron-deficient (FeD) diet, the vitamin A- and iron-deficient (VAFeD) diet or the diet with 12 mg atRA/kg diet replacing all-trans-retinyl palmitate by all-trans retinoic acid (atRA). Vitamin A deficiency reduced serum iron and transferrin saturation levels, increased spleen iron concentrations, reduced hepatic Hamp and kidney erythropoietin messenger RNA (mRNA) levels and up-regulated hepatic and spleen heme oxygenase-1 gene expression while reducing the liver HO-1 specific activity compared with the control. The FeD and VAFeD rats exhibited lower levels of serum iron and transferrin saturation, lower iron concentrations in tissues and lower hepatic Hamp mRNA levels compared with the control. The treatment with atRA resulted in lower serum iron and transferrin concentrations, an increased iron concentration in the liver, a decreased iron concentration in the spleen and in the gut, and decreased hepatic Hamp mRNA levels. In summary, these findings suggest that vitamin A deficiency leads to ineffective erythropoiesis by the down-regulation of renal erythropoietin expression in the kidney, resulting in erythrocyte malformation and the consequent accumulation of the heme group in the spleen. Vitamin A deficiency indirectly modulates systemic iron homeostasis by enhancing erythrophagocytosis of undifferentiated erythrocytes.
authors.affiliation: Postgraduate Program in Human Nutrition, Faculty of Health Sciences, Campus Universitário Darcy Ribeiro, Universidade de Brasília, P.O. Box 70910-900, Brasília, DF, Brazil. Electronic address: desa.marcela@gmail.com.
authors.forename: Marcela S B
authors.initials: MS
authors.lastname: da Cunha
authors.affiliation: Cell Biology Department of Biological Sciences Institute, Campus Universitário Darcy Ribeiro, Universidade de Brasília, P.O. Box 70910-900, Brasília, DF, Brazil.
authors.forename: Egle M A
authors.initials: EM
authors.lastname: Siqueira
authors.affiliation: Nutrition Department of Health Sciences Faculty, Campus Universitário Darcy Ribeiro, Universidade de Brasília, P.O. Box 70910-900, Brasília, DF, Brazil.
authors.forename: Luciano S
authors.initials: LS
authors.lastname: Trindade
authors.affiliation: Postgraduate Program in Human Nutrition, Faculty of Health Sciences, Campus Universitário Darcy Ribeiro, Universidade de Brasília, P.O. Box 70910-900, Brasília, DF, Brazil.
authors.forename: Sandra F
authors.initials: SF
authors.lastname: Arruda
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004912:Erythrocytes / Q000378:metabolism; D004920:Erythropoiesis; D004921:Erythropoietin / Q000097:blood / Q000235:genetics; D005819:Genetic Markers; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D064451:Hepcidins / Q000097:blood / Q000235:genetics; D006706:Homeostasis; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007501:Iron / Q000097:blood*; D000090463:Iron Deficiencies; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D015854:Up-Regulation; D014801:Vitamin A / Q000008:administration & dosage / Q000097:blood*; D014802:Vitamin A Deficiency / Q000097:blood*; D000098742:Ferroportin
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D005819:Genetic Markers; C578703:Hamp protein, rat; D064451:Hepcidins; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014168:Transferrin; D000098742:Ferroportin; D004921:Erythropoietin; D014801:Vitamin A; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Erythropoietin (Epo); Heme oxygenase-1 (Hmox1); Hepcidin; Iron homeostasis; Vitamin A deficiency