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Adiponectin receptor 1 (AdipoR1) is a key metabolic receptor primarily expressed in skeletal muscle and adipose tissue, where it serves as a high-affinity receptor for globular adiponectin and a low-affinity receptor for full-length adiponectin. Unlike classical G protein-coupled receptors, AdipoR1 possesses an inverted membrane topology with an internal N-terminus and an external C-terminus. Its activation triggers the phosphorylation of AMP-activated protein kinase (AMPK) and the activation of PPAR-alpha, leading to increased fatty acid oxidation and glucose uptake, which collectively improve systemic insulin sensitivity. In pathological states such as obesity and type 2 diabetes, adiponectin levels and receptor expression are often downregulated, contributing to the development of insulin resistance and metabolic dysfunction. Consequently, AdipoR1 has emerged as a significant therapeutic target for metabolic disorders. Small-molecule agonists like AdipoRon have demonstrated the potential to mimic the beneficial effects of adiponectin, offering a promising strategy for treating obesity-related diseases and nonalcoholic fatty liver disease. While the term "Adipocyte receptor" is sometimes used generically to refer to various receptors on fat cells (including Beta-3 adrenergic receptors or ACVR1C), it most frequently identifies the adiponectin receptor system in modern metabolic research.
Agonism of AdipoR1 activates the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR-alpha) signaling pathways, which enhances glucose uptake and fatty acid oxidation while suppressing gluconeogenesis.
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