Aryl hydrocarbon receptor: a multifaceted environmental sensor in liver homeostasis and disease.

The aryl hydrocarbon receptor (AhR) functions as a pivotal integrator of environmental and metabolic signals, playing a complex and highly context-dependent dual role in liver homeostasis and injury. On one hand, by sensing exogenous toxins or specific endogenous ligands, it can mediate mitochondrial dysfunction, oxidative stress, DNA damage, and aberrant metabolic activation, thereby driving hepatocyte apoptosis, steatosis, and inflammatory responses, which contributes to the initiation and progression of liver damage. On the other hand, AhR can also elicit hepatoprotective effects by responding to distinct ligand signals. These protective mechanisms include the inhibition of activation and fibrogenesis in hepatic stellate cells, the induction of anti-inflammatory phenotypes in immune cells, and the regulation of bile acid and lipid metabolic homeostasis. This review aims to summarize recent advances in understanding the role of AhR in liver injury, with a focus on dissecting the underlying mechanisms for its seemingly paradoxical functions. The insights provided herein are expected to offer a theoretical foundation and future research directions for exploring AhR-targeted intervention strategies in liver diseases.