Isoginkgetin enhances adiponectin secretion from differentiated adiposarcoma cells via a novel pathway involving AMP-activated protein kinase

Adiponectinisananti-diabetichormonesecretedbyadipocytes. Circulating adiponectin levels are lower in obese and type II diabetic patients than in healthy people. Weight loss or thiazolidinedionetreatmentincreasesplasmaadiponectinlevels. Animal models and human studies suggest that elevated adiponectin levels increase insulin sensitivity. We screened a library of drug-like compounds and natural products for novel agents enhancing adiponectin production. We identified isoginkgetin, a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectinproduction.However,unlikerosiglitazone,peroxisome proliferators-activated receptor g activity seems not required for the action of isoginkgetin, and isoginkgetin has onlya slight effect on adipogenesis, which makes it an attractive candidate for anti-diabetic treatment. Further investigation revealedthatbothisoginkgetinandrosiglitazoneactivateAMPactivated protein kinase (AMPK) in adipocytes. Our findings suggest a novel mechanism for the elevation of adiponectin by isoginkgetin, which is different from that of rosiglitazone. Furthermore, this novel mechanism for adiponectin regulation involvingAMPKcanpotentiallyfacilitatenewunderstandingof metabolic diseases and identification of new targets, as well as agents that increase plasma adiponectin levels.