Isoginkgetin enhances adiponectin secretion from differentiated adiposarcoma cells via a novel pathway involving AMP-activated protein kinase.
Adiponectin is an anti-diabetic hormone secreted by adipocytes. Circulating adiponectin levels are lower in obese and type II diabetic patients than in healthy people. Weight loss or thiazolidinedione treatment increases plasma adiponectin levels. 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 adiponectin production. However, unlike rosiglitazone, peroxisome proliferators-activated receptor gamma activity seems not required for the action of isoginkgetin, and isoginkgetin has only a slight effect on adipogenesis, which makes it an attractive candidate for anti-diabetic treatment. Further investigation revealed that both isoginkgetin and rosiglitazone activate AMP-activated 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 involving AMPK can potentially facilitate new understanding of metabolic diseases and identification of new targets, as well as agents that increase plasma adiponectin levels.
Liu
Guohong
G
Immusol Inc., 10790 Roselle Street, San Diego, California 92121, USA.
Grifman
Mirta
M
Macdonald
James
J
Moller
Peter
P
Wong-Staal
Flossie
F
Li
Qi-Xiang
QX
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects; D052242:Adiponectin / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D015854:Up-Regulation
D052242:Adiponectin; D044946:Biflavonoids; D005419:Flavonoids; D007004:Hypoglycemic Agents; D009097:Multienzyme Complexes; D047495:PPAR gamma; D045162:Thiazolidinediones; C452984:isoginkgetin; D000077154:Rosiglitazone; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases