2. Academic Validation
  3. Transferrin receptor 1-mediated iron uptake supports thermogenic activation in human cervical-derived adipocytes

Transferrin receptor 1-mediated iron uptake supports thermogenic activation in human cervical-derived adipocytes

  • FEBS Lett. 2026 Feb 28. doi: 10.1002/1873-3468.70312.
Rahaf Alrifai 1 2,  Mizuki Seo 1 2,  Gyath Karadsheh 1 2,  Fachrur Rizal Mahendra 3 4,  Máté Á Demény 5,  Ferenc Győry 6,  János András Mótyán 7,  László Fésüs 1,  Endre Kristóf 1,  Rini Arianti 1
Affiliations

Affiliations

  • 1 Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  • 2 Doctoral School of Molecular Cellular and Immune Biology, University of Debrecen, Debrecen, Hungary.
  • 3 Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia.
  • 4 Bioinformatics Research Center, Indonesian Institute of Bioinformatics (INBIO Indonesia), Malang, Indonesia.
  • 5 Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  • 6 Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  • 7 Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
PMID: 41761895 DOI: 10.1002/1873-3468.70312
Abstract

Adrenergic-driven thermogenic activation of brown adipose tissue requires high amounts of nutrients including iron to support mitochondrial biogenesis. This is governed by rapid gene expression changes in ex vivo differentiated human cervical-derived brown adipocytes. Transferrin Receptor 1 (TFRC) is upregulated in response to dibutyryl-cAMP. We aim to investigate the mechanism of facilitated iron uptake when thermogenesis is activated. Pharmacological inhibition and siRNA-mediated knock-down of TFRC during stimulation decrease intracellular iron content and prevent elevation of oxygen consumption and induction of thermogenic markers. Deferoxamine-mediated iron chelation also shows comparable effects. Contrarily, the expression of Ferroportin exporter is suppressed during activation; however, its inhibition does not increase thermogenesis. Brown adipocytes constitutively express and secrete high amounts of transferrin, while melanotransferrin expression and release are upregulated only in activated adipocytes. In silico analysis suggests that melanotransferrin interacts with the helical domain of TFRC. Our findings support that iron is critical in stimulating adipocyte thermogenesis.

Keywords

human cervical‐derived adipocytes; iron uptake; melanotransferrin; mitochondrial biogenesis; thermogenic activation; transferrin; transferrin receptor.

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