Abstract

Background : Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a globally prevalent hepatic disorder, characterized by hepatic lipid accumulation and extrahepatic complications, notably intestinal barrier injury, which further exacerbates MASLD progression. The “gut–liver axis” has been identified as a critical contributor to MASLD development, with insulin-like growth factor 1 (IGF-1) serving as a pivotal coupling factor of this axis. However, the specific role and molecular mechanism by which IGF-1 modulates intestinal barrier function in the context of MASLD remains unclear. Methods : This study analyzed the correlations between the GH/IGF-1 axis and intestinal barrier function in MASLD rats, and explored the effects of IGF-1 intervention both in vivo and in vitro. Results : Our results showed that MASLD rats exhibited intestinal barrier impairment, characterized by elevated serum Diamine oxidase (DAO) and D-Lactate (D-LAC) levels, villus damage, and downregulation of tight junction proteins and Mucin (MUC2). These changes were accompanied by suppression of the GH/IGF-1 axis. Correlation analysis uncovered a negative association between IGF-1 levels and markers of barrier dysfunction. IGF-1 intervention effectively repaired the intestinal barrier structure of MASLD rats and significantly upregulated the expressions of IGF-1R, PI3K, and AKT. In vitro, IGF-1 treatment improved transepithelial electrical resistance (TEER), enhanced barrier-related gene expression, promoted cell proliferation, and inhibited apoptosis. Conclusions : These findings suggested that GH/IGF-1 axis suppression, intestinal barrier dysfunction, and IGF-1R/PI3K/AKT signaling were interconnected within the gut–liver axis in MASLD. IGF-1 may contribute to barrier regulation through associated signaling changes, highlighting the GH/IGF-1 axis as a potential complementary target.