Ablation of hephaestin and ceruloplasmin results in iron accumulation in adipocytes and type 2 diabetes.

Abstract

Little is known about the iron efflux mechanism in adipocytes. Here, we used hephaestin (Heph) and ceruloplasmin (Cp) single-knockout (KO) mice and Heph/Cp double-KO mice to investigate the roles of multicopper ferroxidases (MCFs) in this process. We show that both HEPH and CP are expressed in subcutaneous adipose tissue. Ablation of either MCF leads to a compensatory increase in the other, which contributes to the balance of iron status. However, ablation of both MCFs together induces severe iron deposition in adipocytes which is associated with decreased adiponectin and leptin mRNA expression. Furthermore, Heph/Cp KO mice display disordered carbohydrate metabolism characterized as type 2 diabetes. Together, these results demonstrate the protective roles of HEPH and CP in preventing iron overload in adipocytes.

• Authors: Jiashuo Zheng, Min Chen, Guohao Liu, En Xu, Huijun Chen
• Journal: FEBS letters (FEBS Lett) Vol. 592 Issue 3 Pg. 394-401 (02 2018) ISSN: 1873-3468 [Electronic] England
• PMID: 29355933 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Federation of European Biochemical Societies.

Chemical References

• Adiponectin
• Adipoq protein, mouse
• Heph protein, mouse
• Leptin
• Membrane Proteins
• Iron
• Ceruloplasmin

Topics

• Adipocytes (metabolism)
• Adiponectin (genetics)
• Animals
• Ceruloplasmin (genetics, metabolism)
• Diabetes Mellitus, Type 2 (genetics, metabolism, veterinary)
• Gene Knockout Techniques
• Iron (metabolism)
• Leptin (genetics)
• Male
• Membrane Proteins (genetics, metabolism)
• Mice