Chronic intermittent hypobaric hypoxia improves iron metabolism disorders via the IL-6/JAK2/STAT3 and Epo/STAT5/ERFE signaling pathways in metabolic syndrome rats.
Chronic intermittent hypobaric hypoxia
Epo/STAT5/ERFE signaling pathway
IL-6/JAK2/STAT3 signaling pathway
Iron metabolism
Metabolic syndrome
Journal
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
ISSN: 1878-3252
Titre abrégé: J Trace Elem Med Biol
Pays: Germany
ID NLM: 9508274
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
11
01
2023
revised:
09
06
2023
accepted:
28
06
2023
medline:
7
8
2023
pubmed:
7
7
2023
entrez:
6
7
2023
Statut:
ppublish
Résumé
Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) improved iron metabolism disorder in obese rats through the downregulation of hepcidin. This study aimed to observe the molecular mechanism of CIHH in improving iron metabolism disorders, especially by Janus kinase/signal transducer and activation of the transcription (JAK/STAT) signaling pathway in metabolic syndrome (MS) rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: CON, CIHH (subjected to hypobaric hypoxia simulating 5000-m altitude for 28 days, 6 h daily), MS (induced by high fat diet and fructose water), and MS+CIHH. The serum levels of glucose, lipid metabolism, iron metabolism, interleukin-6 (IL-6), erythropoietin (Epo) and hepcidin were measured. The protein expressions of JAK2, STAT3, STAT5, bone morphogenetic protein 6 (BMP6), small mothers against decapentaplegic 1 (SMAD1) and hepcidin were examined. The mRNA expressions of erythroferrone (ERFE) and hepcidin were analyzed. The MS rats displayed obesity, hyperglycemia, hyperlipidemia, iron metabolism disorder, increased IL-6 and hepcidin serum levels, upregulation of JAK2/STAT3 signaling pathway, decreased Epo serum levels, downregulation of STAT5/ERFE signaling pathway in spleen, upregulation of BMP/SMAD signaling pathway in liver, and increased hepcidin mRNA and protein expression compared to CON rats. All the aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats. CIHH improved iron metabolism disorders, possibly by inhibiting IL-6/JAK2/STAT3 and activating Epo/STAT5/ERFE signaling pathway, thus downregulating hepcidin in MS rats.
Identifiants
pubmed: 37413927
pii: S0946-672X(23)00135-9
doi: 10.1016/j.jtemb.2023.127259
pii:
doi:
Substances chimiques
Interleukin-6
0
Hepcidins
0
STAT5 Transcription Factor
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127259Informations de copyright
Copyright © 2023 Elsevier GmbH. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.