AdipoR1

AdipoR1, or adiponectin receptor 1, is a protein encoded by the human ADIPOR1 gene. It belongs to the adiponectin receptor family, which also includes AdipoR2, and functions as a cell-surface receptor for adiponectin, a hormone produced by adipose tissue that regulates glucose and lipid metabolism. Unlike classical G protein–coupled receptors, AdipoR1 and AdipoR2 have seven transmembrane domains with the N-terminus oriented toward the cytosol, placing them in the “reverse” topology relative to many GPCRs.

AdipoR1 is widely expressed, with particularly high levels in skeletal muscle, while AdipoR2 shows greater expression in the liver. Adiponectin exists in several forms, including full-length adiponectin and a globular fragment. Globular adiponectin preferentially binds AdipoR1, whereas full-length adiponectin has higher affinity for AdipoR2; nonetheless, both receptors can mediate signaling in response to adiponectin.

Signaling through AdipoR1 and AdipoR2 mediates distinct metabolic pathways. Activation of AdipoR1 is commonly linked to the AMP-activated protein kinase (AMPK) pathway, promoting glucose uptake and fatty acid oxidation. AdipoR2 signaling is associated with the peroxisome proliferator-activated receptor alpha (PPAR-α) pathway, also enhancing lipid oxidation. Some studies have reported intrinsic ceramidase activity for AdipoR1 and AdipoR2, connecting adiponectin signaling to sphingolipid metabolism. AdipoR1 and AdipoR2 can interact with adaptor proteins such as APPL1 to propagate downstream signals.

Clinical relevance for AdipoR1 includes its role in maintaining insulin sensitivity and energy homeostasis. Reduced adiponectin signaling is associated with obesity and insulin resistance in experimental models, highlighting these receptors as potential targets for metabolic disease therapies.