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Adiponectin receptor 1; Adiponectin receptor 2 (AdipoR1; AdipoR2)
- Target
- AdipoR1; AdipoR2
- Molecular classification
- Receptor (cell surface), Progestin and adipoQ receptor (PAQR) family, Seven-transmembrane (7TM) domain receptor, Distinct from classical G protein-coupled receptors (GPCRs) — inverted orientation, no G protein coupling
01
Overview
Adiponectin receptor 1 and 2 are seven-transmembrane domain receptors unrelated to classical GPCRs, mainly expressed on skeletal muscle (AdipoR1) and liver (AdipoR2) cells. They mediate the metabolic actions of adiponectin, especially enhancing insulin sensitivity, fatty acid oxidation, and glucose uptake, mainly via AMPK and PPAR-α pathways. They play critical roles in metabolic, inflammatory, and fibrotic diseases, and are considered important pharmacological targets for the treatment of type 2 diabetes, NASH, and obesity-related complications. Various peptide and small-molecule agonists have been developed to target these receptors with the goal of restoring metabolic balance and protecting tissues from inflammation and apoptosis.
- Other names
- PAQR1PAQR2
02
Mechanism of action
Direct agonism of AdipoR1/AdipoR2 stimulates downstream signaling pathways: AMPK (AdipoR1), PPAR-α (AdipoR2), PI3K-Akt (AdipoR1). Ceramidase activity reduces intracellular ceramide, mitigating apoptosis and inflammation. Modulation of mitochondrial function (via AMPK and PPAR-α regulation).
03
Biological functions
Signal transductionGlucose and lipid metabolism regulationInsulin sensitivity modulationFatty acid oxidationRegulation of oxidative stressCeramide metabolism (ceramidase activity)Anti-inflammatory signalingCell proliferation and apoptosis regulation (via PI3K-Akt pathway)
04
Disease associations
Type 2 diabetesObesityCardiovascular diseaseNonalcoholic fatty liver disease (NAFLD)/NASHVarious cancersNeurodegenerative disease (Alzheimer’s)InflammationFibrosis (liver and systemic)
05
Safety considerations
Limited data; theoretical concerns could include off-target metabolic effects or interference with critical homeostatic pathwaysNo major class-specific safety liabilities yet published; tight metabolic regulation required due to broad downstream effects
06
Interacting drugs
AdipoRon
9 more in the full profile.
07
Biomarkers
Expression levels of ADIPOR1 and ADIPOR2 genes/proteinsCirculating adiponectin levels
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