Adiponectin receptor 1 (AdipoR1) and Adiponectin receptor 2 (AdipoR2) (AdipoR1, AdipoR2)

The adiponectin receptors—adiponectin receptor 1 (**AdipoR1**) and adiponectin receptor 2 (**AdipoR2**)—are integral membrane proteins that mediate the effects of the hormone adiponectin. They belong to a unique class within the seven-transmembrane domain protein superfamily but have a topology opposite that of G-protein-coupled receptors. Both possess an internal cavity coordinating a zinc ion within their transmembrane domains—a feature linked with their intrinsic but low ceramidase enzymatic activity. AdipoR1 is highly expressed in skeletal muscle while AdipoR2 predominates in liver tissue; both are widely distributed across other tissues. Upon activation by either endogenous adiponectin or synthetic agonists like AdipoRon, they regulate key metabolic processes including glucose uptake/utilization via AMP kinase activation and fatty acid oxidation through PPARα signaling. These functions make them central players in maintaining insulin sensitivity and energy balance; dysfunction contributes significantly to type 2 diabetes mellitus, obesity-related disorders, cardiovascular disease, NAFLD, and potentially inflammatory conditions. While no approved drugs currently target these receptors directly for human therapy, the development pipeline includes several small-molecule agonists aimed at harnessing their beneficial metabolic actions for treating complex chronic diseases associated with impaired glucose/lipid homeostasis.[4][7][5]

Other names

ADIPOR1ADIPOR2PAQR1 (for AdipoR1)PAQR2 (for AdipoR2)Progesterone and adiponectin Q receptor family membersSometimes collectively referred to as "adiponectin receptors"

Drugs targeting these receptors act primarily as **agonists**, mimicking the action of endogenous adiponectin by binding to the receptors and activating downstream signaling pathways such as AMPK activation, increased fatty acid oxidation, reduced gluconeogenesis, improved insulin sensitivity, and enhanced ceramidase activity leading to decreased cellular ceramide levels.[3]