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

• Published in: Nutrients Vol. 12; no. 5; p. 1515
• Main Authors: Arruda, Sandra Fernandes, Ramos, Larissa Valadares, Barbosa, Júlia Lima de Alencar, Hankins, Natália Aboudib Campos, Rodrigues, Pedro Augusto Matos, Cunha, Marcela de Sá Barreto da
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 22-05-2020; MDPI AG
• Subjects: Animals; Antigens, CD; Arecaceae - chemistry; Bone Morphogenetic Protein 6 - metabolism; Brazil; Diet; Fruit - chemistry; Gene Expression Regulation; hepcidin; Hepcidins - metabolism; iron; Iron - metabolism; Iron Overload; Liver - metabolism; Male; pSMAD1/5/8; pSTAT3; Rats; Rats, Wistar; Receptors, Transferrin; RNA, Messenger; Signal Transduction - physiology; Sirtuin 1 - metabolism; Smad1 Protein - metabolism; Smad5 Protein; Smad7 Protein; Smad8 Protein; STAT3 Transcription Factor - metabolism; tucum-do-cerrado; Brazil; pSMAD1/5/8; pSTAT3; iron; hepcidin; tucum-do-cerrado
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12051515

The Brazilian savanna fruit, tucum-do-cerrado (
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
mRNA levels but did not alter
,
,
, and
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
mRNA levels, as well as pSMAD1/5/8 and pSTAT3 protein levels, while no difference was observed in
,
,
,
, and
mRNA levels and LIP compared to the CT group. The association of tucum-do-cerrado with the iron-enriched diet (Tuc+Fe) decreased
,
,
, and
mRNA levels and pSTAT3 protein content compared to the +Fe group, while increased
and decreased
mRNA levels compared to the Tuc group. Therefore, the inhibition of hepatic hepcidin by tucum-do-cerrado consumption may involve the downregulation of intestinal
and hepatic
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.