AdipoR2

AdipoR2, or adiponectin receptor 2, is a seven-transmembrane receptor encoded by the ADIPOR2 gene in humans. It is one of two known adiponectin receptors, along with ADIPOR1, that mediate the metabolic effects of adiponectin, a hormone produced by adipose tissue with insulin-sensitizing and anti-inflammatory properties.

Expression of AdipoR2 is highest in the liver, with detectable levels in adipose tissue, skeletal muscle, and other organs. Biochemically, AdipoR2 shares the adiponectin-binding function of its family, but it has an unusual membrane topology compared to classical G protein-coupled receptors. Binding of adiponectin initiates intracellular signaling via adapters such as APPL1, leading to activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR-α) pathways, which promote fatty acid oxidation and improve insulin sensitivity. In addition, adiponectin receptors including AdipoR2 have been reported to possess intrinsic ceramidase activity, lowering ceramide levels and contributing to metabolic benefits.

Physiological roles of AdipoR2 include regulation of hepatic glucose and lipid metabolism. In the liver, receptor activation reduces gluconeogenesis and increases fatty acid oxidation; studies in animals show that AdipoR2 deficiency can exacerbate hepatic steatosis. In muscle and adipose tissue, AdipoR2 signaling participates in glucose uptake and lipid handling, supporting systemic insulin sensitivity.

Clinical relevance of ADIPOR2 includes associations of genetic variation with lipid traits and insulin sensitivity in certain populations. Altered AdipoR2 expression has been observed in obesity and type 2 diabetes, and the receptor is studied as a potential therapeutic target. Researchers are exploring adiponectin receptor agonists to mimic endogenous signaling.