title: Vanadyl acetylacetonate upregulates PPARγ and adiponectin expression in differentiated rat adipocytes.
abstract: Vanadium compounds are promising agents in the therapeutic treatment of diabetes mellitus, but their mechanism of action has not been fully elucidated. The current work investigated the effects of vanadyl acetylacetonate, VO(acac)2, on peroxisome-proliferator-activated receptor γ (PPARγ) and adiponectin, which are important targets of antidiabetic drugs. The experimental results revealed that vanadyl complexes increased the expression and multimerization of adiponectin in differentiated rat adipocytes. VO(acac)2 caused activation of p38 mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) and elevation of PPARγ levels. The specific inhibitors SB203580 (p38 MAPK inhibitor) and T0070907 (PPARγ inhibitor) decreased the expression of adiponectin; however, compound C (AMPK inhibitor) did not significantly reduce the expression of adiponectin. In addition, vanadyl complexes induced protein-protein interaction between PPARγ and a vanadium-binding chaperone, heat shock protein 60 kDa. Overall, our results suggest that vanadyl complexes may upregulate PPARγ by suppressing PPARγ degradation, and thus stimulate adiponectin expression and multimerization. The present work has provided new insights into the mechanism of the antidiabetic actions of vanadium compounds.
authors.affiliation: State Key Laboratories of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, PR China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Wu
authors.forename: Meiling
authors.initials: M
authors.lastname: Huang
authors.forename: Pan
authors.initials: P
authors.lastname: Zhao
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Yang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D010422:Pentanones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D052242:Adiponectin; D006885:Hydroxybutyrates; D047495:PPAR gamma; D010422:Pentanones; C049529:acetyl acetonate; D048051:p38 Mitogen-Activated Protein Kinases