Insulin-like Growth Factor 1 Ameliorates Intestinal Barrier Dysfunction in MASLD via IGF-1R/PI3K/AKT Signaling

Area of Science:

• Hepatology
• Gastroenterology
• Endocrinology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder linked to intestinal barrier injury.
• The gut-liver axis plays a key role in MASLD, with insulin-like growth factor 1 (IGF-1) as a critical mediator.
• The precise role of IGF-1 in MASLD-related intestinal barrier dysfunction is not fully understood.

Purpose of the Study:

• To investigate the relationship between the growth hormone/IGF-1 axis and intestinal barrier function in MASLD.
• To explore the therapeutic potential of IGF-1 intervention in MASLD-induced gut barrier damage.

Main Methods:

• Analysis of MASLD rat models to correlate GH/IGF-1 axis status with intestinal barrier integrity.
• In vivo and in vitro experiments to assess the effects of IGF-1 administration on gut barrier parameters.
• Measurement of serum markers (DAO, D-LAC), histological analysis, and assessment of tight junction proteins and MUC2 expression.

Main Results:

• MASLD rats displayed impaired intestinal barriers, evidenced by elevated DAO/D-LAC, villus damage, and reduced tight junction proteins/MUC2.
• A suppressed GH/IGF-1 axis was observed in MASLD rats, with lower IGF-1 levels correlating with barrier dysfunction.
• IGF-1 treatment in vivo and in vitro successfully repaired intestinal barrier structure, enhanced barrier function markers, and modulated the IGF-1R/PI3K/AKT signaling pathway.

Conclusions:

• The GH/IGF-1 axis, intestinal barrier function, and IGF-1R/PI3K/AKT signaling are interconnected in the gut-liver axis of MASLD.
• IGF-1 demonstrates potential for regulating intestinal barrier integrity in MASLD.
• The GH/IGF-1 axis emerges as a promising complementary therapeutic target for MASLD.