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Modulation of hepcidin synthesis: the core link in the bi-directional relationship between iron and obesity

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Over the past five decades, clinical and experimental data have established that iron metabolism, lipid metabolism, and obesity are intricately linked and differentially influence one another through complex metabolic pathways. Iron dyshomeostasis is now recognized as a key modulator of lipid metabolism, with profound implications for obesity and related metabolic disorders. Likewise, lipid metabolism and obesity significantly impact iron absorption and recycling. Although this interplay between iron metabolism, lipid metabolism, and obesity is complex, modulation of hepcidin synthesis seems to be the core link between these variables. As the global prevalence of metabolic disorders continues to escalate, understanding their multifactorial etiology has become a public health priority. Emerging evidence highlights the dysregulation of lipid metabolism as a central driver in the onset and progression of these conditions, with iron metabolism playing a crucial regulatory role. This review explores the relationship between iron metabolism on one hand and lipid metabolism and obesity on the other with specific emphasis on the molecular mechanisms underlying this relationship. The review also explores the bi-directional relationship between iron metabolism and mitochondrial functions, mainly energy production. It concludes by outlining the pathophysiological consequences of disrupted iron metabolism, vis-a-vis lipid metabolism, obesity, and diabetes. By synthesizing current knowledge, this review aims to provide new insights that could guide the development of novel therapeutic strategies to manage obesity, diabetes, and related metabolic disorders.

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Acknowledgements

The authors wish to acknowledge the generous in-house support of the Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, UAE.

Funding

This work was supported by research grant 2101050170 (MH), University of Sharjah, Sharjah, UAE, and the Iron Biology Research Group operation budget, the Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, UAE.

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Authors and Affiliations

  1. Iron Biology Research Group, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates

    Bilal Rah, Rumaisa Rafiq, Jasmine Sharafain, Jalal Taneera & Mawieh Hamad

  2. Department of Biomedical Sciences, Birmingham Medical School, University of Birmingham, Edgbaston, Birmingham, UK

    Jibran Sualeh Muhammad

  3. Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates

    Jalal Taneera

  4. Department of Medical Laboratory Technology, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates

    Mawieh Hamad

  5. Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, UAE

    Mawieh Hamad

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  1. Bilal Rah
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Contributions

Conceptualization, MH; methodology, MH, RH, RR, JS; original draft preparation, BR, RR, and MH; reviewing and editing, MH, JSM, JT, JR. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Mawieh Hamad.

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Rah, B., Rafiq, R., Sharafain, J. et al. Modulation of hepcidin synthesis: the core link in the bi-directional relationship between iron and obesity. Rev Endocr Metab Disord (2025). https://doi.org/10.1007/s11154-025-09997-y

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