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Review
. 2025 Jul 4:16:1581632.
doi: 10.3389/fphar.2025.1581632. eCollection 2025.

Ferroptosis as a potential therapeutic target for obesity-related metabolic diseases

Chao-Dong Huang #  1 , Tao Luo #  2 , Hua Zhang #  3   4 , Lin-Hui Cheng  5 , Shu-Hong Peng  6 , Xiao-Wei Zhou  7 , Lan Cao  1 , Fang-You Chen  1 , Jun-Wei He  1 , Chen Chen  8 , Chang-Hua Zhang  1   4 , Yu-Ai Zhang  9 , Ling-Yun Zhong  1
Affiliations
Review

Ferroptosis as a potential therapeutic target for obesity-related metabolic diseases

Chao-Dong Huang et al. Front Pharmacol. .

Abstract

Obesity represents one of the major public health issues threatening the global health and promoting chronic metabolic disorders, including type 2 diabetes, insulin resistance (IR), hyperlipidemia, hypertension, polycystic ovary syndrome, metabolic-associated fatty liver disease (MAFLD), and others. Ferroptosis, a novel form of cell death, is a programmed cell death induced by iron-dependent lipid peroxidation. It is characterized by excessive iron accumulation and unregulated lipid peroxidation. The activity of ferroptosis is modulated by multiple factors such as iron, reactive oxygen species, and over 98 unsaturated fatty acids. Mounting evidence indicates that ferroptosis plays a crucial role in obesity-related chronic metabolic diseases like type 2 diabetes, IR, hyperlipidemia, hypertension, polycystic ovary syndrome, and MAFLD. Clarifying the molecular mechanism of ferroptosis may discover potential therapeutic targets for the treatment of these diseases. This article comprehensively reviews the role, pathogenesis, prevention, treatment strategies, current research gaps and future development directions of ferroptosis in obesity-related chronic metabolic diseases have been thoroughly discussed, and novel perspectives for the future treatment and research of ferroptosis in these diseases carefully provided. It points out directions for basic research on ferroptosis, raises urgent needs for developing precise intervention strategies, and provides new insights into the treatment and study of obesity-related chronic metabolic diseases in the future.

Keywords: ferroptosis; obesity-related metabolic diseases; occurrence and regulation of ferroptosis; pharmacotherapy strategy; potential therapeutic targets.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author CC declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
The occurrence of ferroptosis. Disorders of intracellular iron metabolism led to iron accumulation, and iron in the labile iron pool (LIP) induced Fenton reaction and generate ROS. ROS led to lipid peroxidation, the destruction of membrane structure in cells and eventually caused cell death. (A) Iron accumulation via TfR1 (transferrin receptor 1)/FPN (ferroportin) imbalance; (B) Generation of reactive oxygen species (ROS) via Fenton reaction and mitochondrial dysfunction; (C) ACSL4 (acyl-CoA synthetase long-chain family member 4)/LOX (lipoxygenase)-mediated lipid peroxidation cascade.
FIGURE 2
FIGURE 2
The key systems involved in the regulation of ferroptosis lipid peroxidation in obesity-related chronic metabolic diseases.
FIGURE 3
FIGURE 3
The imbalance between energy intake and energy expenditure leads to obesity and obesity-related metabolic diseases.
FIGURE 4
FIGURE 4
Effect of ferroptosis on the progression of obese liver disease. Liver cells are the main place of iron storage in the body and greatly affected by iron overload. The occurrence of ferroptosis greatly promotes the progression of obese-related fatty liver disease. Ferroptosis of hepatic stellate cell (HSC) and other cells aggravates liver inflammation, fibrosis and eventually HCC.
FIGURE 5
FIGURE 5
The occurrence and regulation of ferroptosis and the targets of related drugs.
See this image and copyright information in PMC

References

    1. Adamska A., Łebkowska A., Krentowska A., Hryniewicka J., Adamski M., Leśniewska M., et al. (2020). Ovarian reserve and serum concentration of thyroid peroxidase antibodies in euthyroid women with different polycystic ovary syndrome phenotypes. Front. Endocrinol. (Lausanne) 11 (undefined), 440. 10.3389/fendo.2020.00440 - DOI - PMC - PubMed
    1. Alberti K., Zimmet P. (2013). Global burden of disease--where does diabetes mellitus fit in? Nat. Rev. Endocrinol. 9 (5), 0. 10.1038/nrendo.2013.54 - DOI - PubMed
    1. Arabpour J., Rezaei K., Khojini J. Y., Razi S., Hayati M. J., Gheibihayat S. M. (2024). The potential role and mechanism of circRNAs in Ferroptosis: a comprehensive review. Pathol. Res. Pract. 255, 155203. 10.1016/j.prp.2024.155203 - DOI - PubMed
    1. Araújo A. R., Rosso N., Bedogni G., Tiribelli C., Bellentani S. (2018). Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: what we need in the future. Liver Int. 38 (Suppl. 1), 47–51. 10.1111/liv.13643 - DOI - PubMed
    1. Arfin S., Agrawal K., Maurya S., Asthana S., Di Silvestre D., Kumar D. (2023). Lead phytochemicals and marine compounds against ceruloplasmin in cancer targeting. J. Biomol. Struct. Dyn. 25, 12703–12719. Published online October. 10.1080/07391102.2023.2272753 - DOI - PubMed

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