TY - JOUR
T1 - Suppression of adipocyte differentiation by 15-methoxypinusolidic acid through inhibition of PPARγ activity
AU - Lee, Ye Seul
AU - Sung, Sang Hyun
AU - Hong, Jeong Ho
AU - Hwang, Eun Sook
N1 - Funding Information:
This work was supported by the R&D program (A080908) funded by Korea Health Industry Development Institute, Korea.
PY - 2010/7
Y1 - 2010/7
N2 - 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 PPARγ, a key adipogenic transcription factor, whereas transcriptional activity of PPARγ was significantly attenuated by 15-MPA. While aP2 promoter activity was increased by ectopic overexpression of PPARγ or by rosiglitazone-induced endogenous PPARγ activation, PPARγ-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 PPARγ-dependent adipogenic gene expression.
AB - 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 PPARγ, a key adipogenic transcription factor, whereas transcriptional activity of PPARγ was significantly attenuated by 15-MPA. While aP2 promoter activity was increased by ectopic overexpression of PPARγ or by rosiglitazone-induced endogenous PPARγ activation, PPARγ-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 PPARγ-dependent adipogenic gene expression.
KW - 15-Methoxypinusolidic acid
KW - Adipocyte differentiation
KW - Pinusolide
KW - PPARγ
UR - http://www.scopus.com/inward/record.url?scp=77955410474&partnerID=8YFLogxK
U2 - 10.1007/s12272-010-0709-0
DO - 10.1007/s12272-010-0709-0
M3 - Article
C2 - 20661713
AN - SCOPUS:77955410474
SN - 0253-6269
VL - 33
SP - 1035
EP - 1041
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
IS - 7
ER -