ORIGINAL RESEARCH article
Front. Nutr.
Sec. Clinical Nutrition
This article is part of the Research TopicIron Across the Lifespan: Absorption, Deficiency, and Clinical TranslationView all articles
Evaluation of FGL1 as a hepatokine marker in iron deficiency
Provisionally accepted
Muhammad Saboor1*
Raghad Abdul Rahim1Shamsah Nabi Dad1Abeer Mohamed Yusuf1Mshael Mohammed Nasser1Hayat Mohsen Mansoor1Adnane Guella2
Noura Alkhayyal2- 1University of Sharjah, Sharjah, United Arab Emirates
- 2University Hospital Sharjah, Sharjah, United Arab Emirates
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Background: Fibrinogen-like protein 1 (FGL1) is a hepatokine that regulates hepcidin through antagonism of the bone morphogenetic protein (BMP) pathway. Although preclinical studies suggest a role for FGL1 in iron metabolism, its clinical behavior in human iron deficiency anemia (IDA) remains unclear. This study evaluates circulating FGL1 levels in IDA and examines its diagnostic performance and relationship with hematologic and biochemical markers. Methods: This cross-sectional study included 112 participants: healthy controls (n = 46), primary IDA (n = 46), and patients with IDA associated with chronic disease (IDA+CD) (n = 20). Hematologic indices, iron parameters, and serum FGL1 were measured. Group comparisons, correlation analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA) were applied to assess diagnostic performance and multivariate biomarker structure. Results: Serum FGL1 concentrations were significantly higher in primary IDA (median 411.2 ng/mL) and IDA+CD (median 292.0 ng/mL) than in healthy controls (median 212.5 ng/mL; p < 0.001). Fibrinogen-like protein 1 did not differ significantly between IDA and IDA+CD (p = 0.106). In primary IDA, FGL1 showed weak correlations with iron markers, whereas in IDA+CD it demonstrated moderate associations with hemoglobinization indices, particularly MCH (r = 0.49). Receiver operating curve analysis showed excellent discrimination between healthy individuals and primary IDA (AUC 0.865) and good discrimination between healthy individuals and all disease groups combined (AUC 0.830). Fibrinogen-like protein 1 performed poorly in distinguishing primary IDA from IDA+CD (AUC 0.357). Principal component analysis showed that FGL1 clustered with classical markers of iron-restricted erythropoiesis along PC1, separating controls from both IDA groups. Conclusion: Fibrinogen-like protein 1 is markedly elevated in iron deficiency and aligns with the broader biochemical signature of iron-restricted erythropoiesis. Its strong ability to distinguish healthy individuals from those with iron deficiency suggests diagnostic potential, particularly when ferritin interpretation is limited.
Keywords: Chronic Disease, fibrinogen-like protein 1 (FGL1), hepatokine, Iron deficiency anemia (IDA), iron metabolism
Received: 14 Dec 2025; Accepted: 11 Feb 2026.
Copyright: © 2026 Saboor, Abdul Rahim, Nabi Dad, Yusuf, Nasser, Mansoor, Guella and Alkhayyal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Muhammad Saboor
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