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Ablation of hephaestin and ceruloplasmin results in iron accumulation in adipocytes and type 2 diabetes
Author(s) -
Zheng Jiashuo,
Chen Min,
Liu Guohao,
Xu En,
Chen Huijun
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12978
Subject(s) - ceruloplasmin , medicine , endocrinology , chemistry , adipose tissue , downregulation and upregulation , adiponectin , diabetes mellitus , biochemistry , biology , insulin resistance , gene
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 ( MCF s) 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 MCF s 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.