Suppression of adipocyte differentiation by 15-methoxypinusolidic acid through inhibition of PPARγ activity.
Pinusolide and its derivative, 15-methoxypinusolidic acid (15-MPA) are diterpenoid compounds isolated from Biota orientalis, which has been used as a Korean folk medicine for treating inflammatory disorders. Pinusolide and 15-MPA suppress nitric oxide generation by suppressing inducible nitric oxide synthase and exerted anti-inflammatory functions, whereas other functions and regulatory mechanisms are largely unknown. In this study, we investigated whether pinusolide and 15-MPA modulate adipocyte differentiation from pre-adipocytes 3T3-L1 cells. We found that 15-MPA, not pinusolide, suppressed adipocyte differentiation in a dose-dependent manner, as revealed by lipid droplet formation and expression of adipogenic genes such as adiponectin and aP2. 15-MPA did not affect mRNA and protein levels of PPARgamma, a key adipogenic transcription factor, whereas transcriptional activity of PPARgamma was significantly attenuated by 15-MPA. While aP2 promoter activity was increased by ectopic overexpression of PPARgamma or by rosiglitazone-induced endogenous PPARgamma activation, PPARgamma-induced aP2 promoter activity was inhibited in the presence of 15-MPA. These results suggest that 15-MPA suppresses adipocyte differentiation through the inhibition of PPARgamma-dependent adipogenic gene expression.
Lee
Ye Seul
YS
Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
Sung
Sang Hyun
SH
Hong
Jeong-Ho
JH
Hwang
Eun Sook
ES
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000502:physiology
C464724:15-methoxypinusolidic acid; D004224:Diterpenes; D006131:Growth Inhibitors; D047495:PPAR gamma