Suppression of adipocyte differentiation by 15-methoxypinusolidic acid through inhibition of PPARγ activity

Ye Seul Lee, Sang Hyun Sung, Jeong Ho Hong, Eun Sook Hwang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1035-1041
Number of pages7
JournalArchives of pharmacal research
Volume33
Issue number7
DOIs
Publication statusPublished - 2010 Jul 1

Keywords

  • 15-Methoxypinusolidic acid
  • Adipocyte differentiation
  • PPARγ
  • Pinusolide

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

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