What question did this study set out to answer?

The research aims to evaluate the clinical behavior of FGL1 as a hepatokine in iron deficiency anemia and its diagnostic performance.

March 8, 2026Open Access

Evaluation of FGL1 as a hepatokine marker in iron deficiency

Key Points

The research aims to evaluate the clinical behavior of FGL1 as a hepatokine in iron deficiency anemia and its diagnostic performance.
Cross-sectional study with 112 participants including healthy controls and two IDA groups.
Measured serum FGL1, hematologic indices, and iron parameters.
Conducted correlation analysis, ROC curves, and principal component analysis to evaluate performance.
FGL1 levels were significantly higher in primary IDA and IDA+CD compared to healthy controls.
Weak correlations with iron markers in primary IDA; moderate associations in IDA+CD with hemoglobinization indices.
High AUC values for distinguishing healthy individuals from primary IDA and combined IDA groups, but poor performance in differentiating between IDA types.

Abstract

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 292.99 ng/ml) than in healthy controls (median 212.49 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.

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Cite This Study

Saboor et al. (Fri,) studied this question.

synapsesocial.com/papers/69ada873bc08abd80d5bb6d1 https://doi.org/https://doi.org/10.3389/fnut.2026.1767385

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