The Action of JAK/STAT3 and BMP/HJV/SMAD Signaling Pathways on Hepcidin Suppression by Tucum-do-Cerrado in a Normal and Iron-Enriched Diets

Nutrients. 2020 May 22;12(5):1515. doi: 10.3390/nu12051515.

Abstract

The Brazilian savanna fruit, tucum-do-cerrado (Bactris setosa Mart.) reduces hepatic hepcidin levels. Therefore, we investigated the effect of tucum-do-cerrado on the TfR/HFE and/or BMP/HJV/SMAD and JAK/STAT pathways, in normal and excess iron conditions. Rats were treated with: control diet (CT); control diet +15% tucum-do-cerrado (Tuc); iron-enriched diet (+Fe); or iron-enriched diet +15% tucum-do-cerrado (Tuc+Fe). Tucum-do-cerrado (Tuc) decreased hepatic Hamp and Hjv mRNA levels but did not alter Bmp6, Smad7, Tfr1, and Hfe mRNA levels; pSMAD1/5/8 and pSTAT3 protein levels; labile iron pool (LIP); and inflammatory biomarkers, compared to the CT group. The iron-enriched diet increased Hamp mRNA levels, as well as pSMAD1/5/8 and pSTAT3 protein levels, while no difference was observed in Hjv, Bmp6, Smad7, Tfr1, and Hfe mRNA levels and LIP compared to the CT group. The association of tucum-do-cerrado with the iron-enriched diet (Tuc+Fe) decreased Hamp, Hjv, Bmp6, and Hfe mRNA levels and pSTAT3 protein content compared to the +Fe group, while increased Hamp and decreased Hfe mRNA levels compared to the Tuc group. Therefore, the inhibition of hepatic hepcidin by tucum-do-cerrado consumption may involve the downregulation of intestinal Dmt1 and hepatic Hjv expression and deacetylation mediated by SIRT1 by a mechanism that is independent of tissue iron content. However, in excess iron conditions, the modulation of hepatic hepcidin expression by tucum-do-cerrado seems to be partially mediated by the inflammatory signaling pathway, as well as involves the chelating activity of tucum-do-cerrado.

Keywords: hepcidin; iron; pSMAD1/5/8; pSTAT3; tucum-do-cerrado.

MeSH terms

  • Animals
  • Antigens, CD
  • Arecaceae / chemistry*
  • Bone Morphogenetic Protein 6 / metabolism
  • Brazil
  • Diet*
  • Fruit / chemistry*
  • Gene Expression Regulation
  • Hepcidins / metabolism*
  • Iron / metabolism*
  • Iron Overload
  • Liver / metabolism*
  • Male
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptors, Transferrin
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / physiology*
  • Sirtuin 1 / metabolism
  • Smad1 Protein / metabolism
  • Smad5 Protein
  • Smad7 Protein
  • Smad8 Protein

Substances

  • Antigens, CD
  • Bone Morphogenetic Protein 6
  • CD71 antigen
  • Hepcidins
  • RNA, Messenger
  • Receptors, Transferrin
  • STAT3 Transcription Factor
  • Smad1 Protein
  • Smad5 Protein
  • Smad7 Protein
  • Smad7 protein, rat
  • Smad8 Protein
  • Iron
  • Sirtuin 1