Advanced Science (Jun 2020)
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,
- Hong Chen,
- Fudi Wang,
- Junxia Min,
- Liwei Xie
Affiliations
- Jin Li
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Xiaohan Pan
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Guihua Pan
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Zijun Song
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Yao He
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Susu Zhang
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Xueru Ye
- Nanfang Hospital Southern Medical University Guangzhou 510515 China
- Xiang Yang
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Enjun Xie
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Xinhui Wang
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Xudong Mai
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Xiangju Yin
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Biyao Tang
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Xuan Shu
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Pengyu Chen
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Xiaoshuang Dai
- BGI Institute of Applied Agriculture BGI‐Shenzhen Shenzhen 518120 China
- Ye Tian
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Liheng Yao
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Mulan Han
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Guohuan Xu
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Huijie Zhang
- Nanfang Hospital Southern Medical University Guangzhou 510515 China
- Jia Sun
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Hong Chen
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- Fudi Wang
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Junxia Min
- The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine Hangzhou 310058 China
- Liwei Xie
- State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University Guangzhou 510070 China
- DOI
- https://doi.org/10.1002/advs.201903366
- Journal volume & issue
-
Vol. 7,
no. 12
pp. n/a – n/a
Abstract
Abstract 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.
Keywords