KMID : 0043320100330071035
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Archives of Pharmacal Research 2010 Volume.33 No. 7 p.1035 ~ p.1041
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Suppression of adipocyte differentiation by 15-methoxypinusolidic acid through inhibition of PPAR¥ã activity
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Lee Ye-Seul
Sung Sang-Hyun Hong Jeong-Ho Hwang Eun-Sook
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Abstract
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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 PPAR¥ã, a key adipogenic transcription factor, whereas transcriptional activity of PPAR¥ã was significantly attenuated by 15-MPA. While aP2 promoter activity was increased by ectopic overexpression of PPAR¥ã or by rosiglitazone-induced endogenous PPAR¥ã activation, PPAR¥ã-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 PPAR¥ã-dependent adipogenic gene expression.
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KEYWORD
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Pinusolide, 15-Methoxypinusolidic acid, PPAR¥ã, Adipocyte differentiation
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