Diagenode

Transferrin Receptor 1 Regulates Thermogenic Capacity and Cell Fate in Brown/Beige Adipocytes


Jin Li, Xiaohan Pan, Guihua Pan, Zijun Song, Yao He, Susu Zhang, Xueru Ye, Xiang Yang, Enjun Xie, Xinhui Wang, Xudong Mai, Xiangju Yin, Biyao Tang, Xuan Shu, Pengyu Chen, Xiaoshuang Dai, Ye Tian, Liheng Yao, Mulan Han, Guohuan Xu, Huijie Zhang, Jia Sun, H

Iron homeostasis is essential for maintaining cellular function in a wide range of cell types. However, whether iron affects the thermogenic properties of adipocytes is currently unknown. Using integrative analyses of multi-omics data, transferrin receptor 1 (Tfr1) is identified as a candidate for regulating thermogenesis in beige adipocytes. Furthermore, it is shown that mice lacking Tfr1 specifically in adipocytes have impaired thermogenesis, increased insulin resistance, and low-grade inflammation accompanied by iron deficiency and mitochondrial dysfunction. Mechanistically, the cold treatment in beige adipocytes selectively stabilizes hypoxia-inducible factor 1-alpha (HIF1α), upregulating the Tfr1 gene, and thermogenic adipocyte-specific Hif1α deletion reduces thermogenic gene expression in beige fat without altering core body temperature. Notably, Tfr1 deficiency in interscapular brown adipose tissue (iBAT) leads to the transdifferentiation of brown preadipocytes into white adipocytes and muscle cells; in contrast, long-term exposure to a low-iron diet fails to phenocopy the transdifferentiation effect found in Tfr1-deficient mice. Moreover, mice lacking transmembrane serine protease 6 (Tmprss6) develop iron deficiency in both inguinal white adipose tissue (iWAT) and iBAT, and have impaired cold-induced beige adipocyte formation and brown fat thermogenesis. Taken together, these findings indicate that Tfr1 plays an essential role in thermogenic adipocytes via both iron-dependent and iron-independent mechanisms.

Tags
Antibody
True MicroChIP kit

Share this article

Published
February, 2020

Source

Products used in this publication

  • ChIP-seq Grade
    C15410005
    H3K9/14ac Antibody
  • ChIP kit icon
    C01010132
    True MicroChIP-seq Kit
  • Mouse IgG
    C15410206
    Rabbit IgG

Events

  • 64th ASH Annual Meeting and Exposition 2022
    New Orleans, Louisiana, USA
    Dec 10-Dec 13, 2022
 See all events

News

 See all news


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics