IGFBPs show dual roles in metabolic dysfunction-associated steatotic liver disease progression

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Frontiers in Medicine Published June 5, 2026 Medically reviewed June 5, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider IGFBPs as potential biomarkers and therapeutic targets in MASLD, but evidence is qualitative.

This is a narrative review that examines the roles of insulin-like growth factor-binding proteins (IGFBPs) in metabolic dysfunction-associated steatotic liver disease (MASLD). The authors synthesize evidence from the literature, focusing on IGFBP1, IGFBP2, IGFBP3, IGFBP5, IGFBP7, IGFBP4, and IGFBP6.

Key findings are qualitative. IGFBP1 and IGFBP2 are reported to confer metabolic protection by promoting lipid oxidation and increasing insulin sensitivity. IGFBP3 and IGFBP5 are described as restraining lipogenesis at early stages but promoting hepatocellular injury and stellate cell activation during fibrosis, indicating dual actions. IGFBP7 is noted to impair insulin signaling, drive ferroptosis, and foster fibrosis, suggesting a pathogenic role. IGFBP4 and IGFBP6 remain less well characterized.

The review does not report specific effect sizes, p-values, or confidence intervals. No limitations are explicitly acknowledged by the authors. The practice relevance is highlighted as their potential as biomarkers for disease staging and as therapeutic targets for interventions. Given the narrative nature, these findings should be interpreted as hypothesis-generating rather than definitive.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that progresses from hepatic steatosis to steatohepatitis, fibrosis, and cirrhosis. While metabolic and inflammatory drivers of disease progression are well recognized, emerging evidence suggests that endocrine modulators, including the insulin-like growth factor binding proteins (IGFBPs), play important roles in MASLD. Beyond their canonical role as insulin-like growth factor (IGF) carriers, IGFBPs act as dynamic regulators of hepatic metabolism, inflammation, and fibrotic remodeling through both IGF-dependent and IGF-independent mechanisms. Growing evidence indicates that IGFBP1 and IGFBP2 confer metabolic protection by promoting lipid oxidation and increasing insulin sensitivity. IGFBP3 and IGFBP5 exhibit dual actions: they restrain lipogenesis at early stages but promote hepatocellular injury and stellate cell activation during fibrosis. IGFBP7 is a predominantly pathogenic modulator that impairs insulin signaling, drives ferroptosis, and fosters fibrosis. By contrast, IGFBP4 and IGFBP6 remain less well characterized. This review integrates recent mechanistic and translational findings on IGFBPs in MASLD with evidence accumulated from recent studies, highlighting their potential as biomarkers for disease staging and as therapeutic targets for interventions.