Insulin-like growth factor binding proteins in metabolic dysfunction-associated steatotic liver disease

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.