Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels

Abstract

BackgroundConsidering that vitamin A deficiency modulates hepcidin expression and consequently affects iron metabolism, we evaluated the effect of vitamin A deficiency in the expression of genes involved in the hemojuvelin (HJV)-bone morphogenetic protein 6 (BMP6)-small mothers against decapentaplegic protein (SMAD) signaling pathway.MethodsMale Wistar rats were treated: control AIN-93G diet (CT), vitamin A-deficient diet (VAD), iron-deficient diet (FeD), vitamin A- and iron-deficient diet (VAFeD), or 12 mg all-trans retinoic acid (atRA)/kg diet.ResultsVitamin A deficiency (VAD) increased hepatic Bmp6 and Hfe2 mRNA levels and down-regulated hepatic Hamp, Smad7, Rarα, and intestinal Fpn1 mRNA levels compared with the control. The FeD rats showed lower hepatic Hamp, Bmp6, and Smad7 mRNA levels compared with those of the control, while in the VAFeD rats only Hamp and Smad7 mRNA levels were lower than those of the control. The VAFeD diet up-regulated intestinal Dmt1 mRNA levels in relation to those of the control. The replacement of retinyl ester by atRA did not restore hepatic Hamp mRNA levels; however, the hepatic Hfe2, Bmp6, and Smad7 mRNA levels were similar to the control. The atRA rats showed an increase of hepatic Rarα mRNA levels and a reduction of intestinal Dmt1 mRNA and Fpn1 levels compared with those of the control.ConclusionsThe HJV-BMP6-SMAD signaling pathway that normally activates the expression of hepcidin in iron deficiency is impaired by vitamin A deficiency despite increased expression of liver Bmp6 and Hfe2 mRNA levels and decreased expression of Smad7 mRNA. This response may be associated to the systemic iron deficiency and spleen iron retention promoted by vitamin A deficiency.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0519-4) contains supplementary material, which is available to authorized users.

Serum Retinol but Not 25(OH)D Status Is Associated With Serum Hepcidin Levels in Older Mexican Adults

“…In contrast, Da Cunha et al [37] found that VAD rats had a lower hepatic HAMP mRNA levels to half those of the control levels and suggested that VAD modulates iron metabolism via ineffective erythropoiesis by down-regulated renal Epo mRNA and up-regulated Hmox1 in the spleen [37]. By using the same protocol in rats, Ribeiro Mendez et al [38] found that VAD up-regulated hepatic Bmp6 and Hfe mRNA levels and down-regulated hepatic HAMP mRNA levels, impairing HJV-BMP6-SMAD signaling pathway that normally activates the expression of hepcidin in ID. Differences in the results between these two studies may be due in part to the rats’ diet treatment, as well as the baseline levels of VA stored in their livers.…”

The positive effect of chick embryo and nutrient mixture on bone marrow- derived mesenchymal stem cells from aging rats

“…Alternative splicing of EIF2A resulted in multiple transcript variants, and affected protein translation and played a deleterious role in aging process 41 , 42 . BMP6 regulated biological processes including iron homeostasis, fat and bone development 43 , 44 . LRP1 was involved in several cellular processes and was decreased in aging 45 .…”

Nutrients, Mitochondrial Function, and Perinatal Health

“…A 50% energy restriction in sheep during the third trimester of pregnancy causes a decrease in mitochondrial function in muscle fibers in adult offspring, as evidenced by the reduction of mitochondrial VO 2max , a lower respiratory coupling ratio, and an increase in the expression of PGC-1α [ 50 ]. In pigs, an energy-restrictive diet during pregnancy (approximately 13% restriction) decreased mtDNA in fetal skeletal muscle, as well as diminished the expression of PGC-1α, sirtuin 1 (SIRT1), NRF-1α (Nuclear Respiration Factor-1α), TFAM, and the β subunit of mitochondrial ATP synthase, when compared with fetuses of mothers with a standard diet during pregnancy [ 51 ].…”