Irisin-mediated hepatic autophagy remodels nutritional metabolism to prevent cognitive dysfunction

Cognitive impairment has emerged as a serious global health challenge and is closely associated with metabolic disorders. Autophagy dysfunction leading to metabolic disorders has become a key factor in neurodegenerative diseases. The liver, as the central organ of systemic metabolism, regulates metabolic homeostasis through hepatic autophagy, thereby affecting the clearance of toxic proteins in the brain and energy supply. Hepatic autophagy dysfunction can increase free fatty acids, which attack the blood-brain barrier and lead to neurodegenerative diseases. Irisin enters the liver via the bloodstream, activates AMPK to promote hepatic autophagy, reduces the production of lipotoxic substances, alleviates neuroinflammation, and ensures effective synaptic signaling. Previous studies have demonstrated that irisin can improve neurodegenerative diseases, but no connection has yet been established between irisin, hepatic autophagy, and cognition. Therefore, this review discusses the positive role of irisin in preventing cognitive impairment through hepatic autophagy. Future studies should employ multi-omics approaches to deeply analyze the metabolic network regulated by irisin and explore its potential in the treatment of neurological diseases. Irisin is expected to serve as a key bridge connecting exercise, metabolic health, and neuroprotection, thus paving the way for the prevention and treatment of cognitive decline and neurodegenerative diseases.