CIRCULATING NEUREGULIN-4 AND FIBROBLAST GROWTH FACTOR-21 IMBALANCE IN IRAQI ADULTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE
1 Department of Chemistry, College of Science, Tikrit University, Tikrit, Iraq,
2 Department of Chemistry, College of Education for Pure Sciences University of Kirkuk, Kirkuk, Iraq.
* Corresponding Author
Research Article
Open Access Research Journal of Science and Technology, 2026, 17(02), 085–098.
Article DOI: 10.53022/oarjst.2026.17.2.0078
Publication history:
Received on 09 July 2026; revised on 16 August 2026; accepted on 18 August 2026
Abstract:
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) involves adipose-tissue dysfunction, hepatic metabolic stress, insulin resistance, and oxidative injury. Neuregulin-4 (NRG4) is an adipose-enriched factor with anti-lipogenic actions, whereas fibroblast growth factor-21 (FGF21) is a predominantly hepatic stress-responsive hormone.
Objective: To compare circulating NRG4 and FGF21 among Iraqi adults with MASLD, obesity without steatosis, and healthy normal-weight controls; examine their associations with metabolic, hepatic, and oxidative-stress variables; and explore the diagnostic performance of an NRG4/FGF21 index.
Methods: This comparative cross-sectional study included 162 adults divided equally among the three study groups. Hepatic steatosis was assessed by FibroScan using the Controlled Attenuation Parameter (CAP). Serum NRG4 and FGF21 were measured by sandwich ELISA, and HOMA-IR, FIB-4, MDA, and TAC were assessed. For the exploratory diagnostic analysis comparing MASLD with obesity without steatosis, the relevant participants were divided into derivation (70%) and internal-validation (30%) subsets.
Results: Across the full sample, NRG4 was lower in MASLD (5.12 ± 1.02 ng/mL) than in obesity without steatosis (6.81 ± 0.92 ng/mL) and healthy controls (8.52 ± 0.85 ng/mL), whereas FGF21 was higher in MASLD (345.2 ± 81.4 pg/mL) than in obesity without steatosis (238.5 ± 65.3 pg/mL) and healthy controls (152.8 ± 74.2 pg/mL); both overall p < 0.001. The NRG4/FGF21 index yielded an AUC of 0.892 (95% CI 0.826-0.951) in the derivation subset and 0.879 (95% CI 0.801-0.942) in the internal-validation subset.
Conclusion: A low-NRG4/high-FGF21 pattern was associated with MASLD beyond the presence of obesity alone. The index showed promising internal discrimination, but prospective external validation and improved assessment of visceral adiposity and liver fat are required before clinical application.
Keywords:
Metabolic Dysfunction-Associated Steatotic Liver Disease; Neuregulin-4; Fibroblast Growth Factor-21; Insulin Resistance; Oxidative Stress; Biomarkers.
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