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Hepcidin‐dependent iron mobilization is required for white to beige adipocyte conversion
Author(s) -
Kim Jiyoung,
Ozaki Grant,
Okla Meshail,
Lee Jaekwon,
Chung Soonkyu
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.637.11
Subject(s) - hepcidin , medicine , endocrinology , thermogenesis , white adipose tissue , thermogenin , transferrin receptor , chemistry , adipose tissue , stimulation , inflammation , downregulation and upregulation , transferrin , biology , biochemistry , gene
Beige adipocytes arise among subcutaneous white adipose tissue (WAT) in response to environmental stimuli such as b‐3 adrenergic receptor (ADRB3) activation. Beige adipocytes are specialized cells for thermogenesis due to the abundance in mitochondria and uncoupling protein 1 (UCP1) expression. Beige adipocytes are named after its brownish tint from mitochondrial‐iron, suggesting that iron metabolism must be coordinated with increased mitochondria during browning. Here, we hypothesized that systemic iron mobilization is necessary for beige conversion. C57BL6 mice were injected with either saline or ADRB3 signaling agonist CL316243 (CL) to stimulate WAT browning. CL injection converted subcutaneous WAT into beige fat evidenced by multilocular morphology, >60‐fold increase of UCP1, and increase of thermogenesis. Hepatic mRNA levels of hepcidin, the hormone that controls iron absorption and its tissue distribution, were decreased by 10‐fold with CL‐injection, suggesting that systemic iron redistribution is involved. Consistently, iron importers including transferrin receptor (TfR) and non‐transferrin‐bound iron importer zinc transporter (ZIP14), were substantially increased in CL‐injected subQ fat. The inhibition hepcidin downregulation by chronic inflammation significantly perturbed WAT browning upon CL stimulation. Furthermore, hepcidin‐deficient mice failed to trigger WAT browning due to lack of iron redistribution signaling. Taken together, this study is the first to demonstrate that hepcidin‐dependent systemic iron redistribution is intimately associated with WAT browning and thermogenic activation