Title
The Thermogenic Characteristics of Adipocytes Are Dependent on the Regulation of Iron Homeostasis
Publication Date
2021
Journal or Book Title
JOURNAL OF BIOLOGICAL CHEMISTRY
Abstract
The development of thermogenic adipocytes concurs with mitochondrial biogenesis, an iron-dependent pathway. Iron regulatory proteins (IRP) 1 and 2 are RNA-binding proteins that regulate intracellular iron homeostasis. IRPs bind to the iron-response element (IRE) of their target mRNAs, balancing iron uptake and deposition at the posttranscriptional levels. However, IRP/IRE-dependent iron regulation in adipocytes is largely unknown. We hypothesized that iron demands are higher in brown/beige adipocytes than white adipocytes to maintain the thermogenic mitochondrial capacity. To test this hypothesis, we investigated the IRP/IRE regulatory system in different depots of adipose tissue. Our results revealed that 1) IRP/IRE interaction was increased in proportional to the thermogenic function of the adipose depot, 2) adipose iron content was increased in adipose tissue browning upon beta 3-adrenoceptor stimulation, while decreased in thermoneutral conditions, and 3) modulation of iron content was linked with mitochondrial biogenesis. Moreover, the iron requirement was higher in HIB1B brown adipocytes than 3T3-L1 white adipocytes during differentiation. The reduction of the labile iron pool (LIP) suppressed the differentiation of brown/beige adipocytes and mitochondrial biogenesis. Using the Fe-59-Tf, we also demonstrated that thermogenic stimuli triggered cell-autonomous iron uptake and mitochondrial compartmentalization as well as enhanced mitochondrial respiration. Collectively, our work demonstrated that IRP/IRE signaling and subsequent adaptation in iron metabolism are a critical determinant for the thermogenic function of adipocytes.
ORCID
Lee, Jaekwon/0000-0003-3179-7334
DOI
https://doi.org/10.1016/j.jbc.2021.100452
Volume
296
License
UMass Amherst Open Access Policy
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Funder
Science, Engineering, and Medicine (SEM) Initiative from University of Nebraska-Lincoln; Nebraska EPSCoR Grant; NIDDK scholarship; [NIH-1P20GM104320]; [R21 HD094273-02]; [DK079209]
Recommended Citation
Yook, Jin-Seon; You, Mikyoung; Kim, Yongeun; Zhou, Mi; Liu, Zhenhua; Kim, Young-Cheul; Lee, Jaekwon; and Chung, Soonkyu, "The Thermogenic Characteristics of Adipocytes Are Dependent on the Regulation of Iron Homeostasis" (2021). JOURNAL OF BIOLOGICAL CHEMISTRY. 239.
https://doi.org/10.1016/j.jbc.2021.100452