Adiponectin and central nervous system disorders: Regulatory mechanisms and therapeutic potential

Adiponectin (APN) is a multifunctional adipokine secreted by adipose tissue that has recently been recognized for its important neuroprotective effects in central nervous system (CNS) disorders. However, effective targeted interventions and the precise molecular mechanisms of APN and its receptors remain incompletely understood. Activation of cerebral APN receptor 1 (AdipoR1) through APN supplementation, APN receptor agonists, or exercise interventions can exert beneficial effects in CNS disorders. These effects are mediated through signaling pathways such as AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPARα), leading to enhanced insulin sensitivity, promotion of autophagic clearance of toxic substances, attenuation of neuroinflammation, reduction of oxidative stress and neuronal apoptosis, and improvement of mitochondrial function. This review summarizes the mechanistic associations between APN and various CNS disorders and analyzes the specific intervention strategies, mechanisms, and therapeutic potential of different APN isoforms, APN receptor agonists, and exercise targeting APN receptors. It provides a theoretical basis for exploring effective therapeutic strategies for CNS disorders. In addition, based on the theoretical rationale that both exercise and APN receptor agonists can independently activate the AdipoR1 signaling pathway, future studies may further explore the synergistic effects and potential value of their combined application, thereby providing new research perspectives for promoting brain health.