Adiponectin

Adiponectin is a 30-kDa adipokine secreted predominantly by white adipocytes, with lower expression in brown adipose tissue and trace expression in other tissues such as placenta and cardiac muscle, and is unique among adipokines in being inversely related to fat mass: levels fall with obesity and visceral adiposity and rise with weight loss, caloric restriction, and aerobic exercise. It circulates as trimers, hexamers, and high-molecular-weight multimers; the high-MW form is considered the most biologically active. Adiponectin signals through AdipoR1 and AdipoR2 receptors to activate AMPK and PPAR-α, improving insulin sensitivity, promoting fatty acid oxidation, suppressing hepatic glucose output, and exerting anti-inflammatory and atheroprotective effects. Low adiponectin is an independent predictor of type 2 diabetes, metabolic syndrome, and cardiovascular disease, and is associated with accelerated biological aging; high levels are observed in centenarians and their offspring.