Heme Oxygenase Induction Suppresses Hepatic Hepcidin and Rescues Ferroportin and Ferritin Expression in Obese Mice

Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron levels by increasing internalization of ferroportin-a transmembrane protein facilitating egress of cellular iron. Chronic low-grade inflammatory states, such as obesity, have been shown to increase oxidative stress and en...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of nutrition and metabolism 2017-01, Vol.2017 (2017), p.1-11
Hauptverfasser: Lakhani, Vishal Hari, Klug, Rebecca, Sodhi, Komal, Peterson, Stephen J., Nawab, Athar, Srikanthan, Krithika, Nichols, Alexandra, Chaudry, Hibba, Sacerdoti, David, Chao, Robert, Arefiev, Yevgeniy, Puri, Nitin, Sharma, Dana
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron levels by increasing internalization of ferroportin-a transmembrane protein facilitating egress of cellular iron. Chronic low-grade inflammatory states, such as obesity, have been shown to increase oxidative stress and enhance hepcidin secretion from hepatocytes and macrophages. Heme-heme oxygenase (HO) is a stress response system which reduces oxidative stress. We investigated the effects of HO-1 induction on hepatic hepcidin levels and on iron homeostasis in hepatic tissues from lean and obese mice. Obese mice exhibited hyperglycemia ( p < 0.05 ); increased levels of proinflammatory cytokines (MCP-1, IL-6, p < 0.05 ); oxidative stress ( p < 0.05 ); and increased hepatic hepcidin levels ( p < 0.05 ). Enhancement of hepcidin was reflected in the reduced expression of ferroportin in obese mice ( p < 0.05 ). However, this effect is accompanied by a significant decline in ferritin expression. Additionally, there are reduced insulin receptor phosphorylation and attenuation of metabolic regulators pAMPK, pAKT, and pLKB1. Cobalt protoporphyrin- (CoPP-) induced HO-1 upregulation in obese mice reversed these alterations ( p < 0.05 ), while attenuating hepatic hepcidin levels. These effects of CoPP were prevented in obese mice concurrently exposed to an inhibitor of HO (SnMP) ( p < 0.05 ). Our results highlight a modulatory effect of HO on iron homeostasis mediated through the suppression of hepatic hepcidin.
ISSN:2090-0724
2090-0732
DOI:10.1155/2017/4964571