Pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3'-kinase.
OBJECTIVE
Thiazolidinediones increase circulating adiponectin. We have previously demonstrated the involvement of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in insulin-stimulated adiponectin secretion. We therefore investigated the effects of the thiazolidinedione pioglitazone on acute adiponectin secretion, and the involvement of the PI3K signaling pathway in this action.


METHODS
We treated murine 3T3-L1 and human primary adipocytes with 1-10 uM pioglitazone for 2 h, +/-PI3K inhibition by Wortmannin (WT). Secreted adiponectin was measured by Western blot. PI3K activity following 15-minute treatments with 1-10 uM pioglitazone was measured by thin layer chromatography. Pioglitazone's effect on adiponectin synthesis and on secretion of newly synthesized adiponectin was studied in 3T3-L1 adipocytes using a pulse-chase technique.


RESULTS
Pioglitazone was found to increase adiponectin secretion and PI3K activity in a dose-dependent manner from 3T3-L1 and human adipocytes. In 3T3-L1 adipocytes, 10 uM pioglitazone increased adiponectin secretion by 84+/-14% (p<0.0001) at 2 h. Similarly, in human adipocytes there was a 56+/-18% (p<0.02) increase in secretion. WT blocked the pioglitazone effect and decreased adiponectin secretion at 2 h (47% of pioglitazone treated, p<0.006). Pioglitazone increased PI3K activity in a dose-dependent manner in both 3T3-L1 (1.7 vs. 2.7-fold increase over control at 2 uM vs. 10 uM dose, p=0.02) and human adipocytes.


CONCLUSIONS
Our data show that pioglitazone acutely stimulates adiponectin secretion from both 3T3-L1 and human adipocytes. This acute effect of pioglitazone is PI3K-dependent.
Pereira
Rocio I
RI
Research Service, Denver Veterans Affairs Medical Center, Denver, CO 80045, United States. rocio.pereira@uchsc.edu
Leitner
J Wayne
JW
Erickson
Christopher
C
Draznin
Boris
B
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic; D000077191:Wortmannin
D052242:Adiponectin; D000730:Androstadienes; D007004:Hypoglycemic Agents; D007329:Insulin Antagonists; D045162:Thiazolidinediones; D019869:Phosphatidylinositol 3-Kinases; D000077205:Pioglitazone; D000077191:Wortmannin