The role of tryptophan-AhR signaling in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD): implications for therapeutic strategies

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a significant global health concern, closely associated with metabolic syndrome and characterized by hepatic fat accumulation, inflammation, and fibrosis. While the pathogenesis of MASLD is multifactorial, recent research has highlighted the role of the tryptophan-aryl hydrocarbon receptor (AhR) signaling pathway in influencing both immune and metabolic functions in the liver. Tryptophan, an essential amino acid, is metabolized into various bioactive metabolites, such as kynurenine, that activate AhR. This activation modulates cellular processes including inflammation, oxidative stress, and lipid metabolism. Emerging evidence suggests that dysregulated tryptophan metabolism and AhR signaling contribute to the progression of MASLD, particularly through immune modulation and alterations in metabolic pathways. This perspective aims to provide an overview of the current understanding of tryptophan-AhR signaling in MASLD, discussing its potential as a therapeutic target and the challenges associated with targeting this pathway. Future research directions are proposed to explore how modulation of the tryptophan-AhR axis could offer novel therapeutic strategies for MASLD, providing new insights into its treatment and management.