Phorbaketal A inhibits adipogenic differentiation through the suppression of PPARγ-mediated gene transcription by TAZ

Mi Ran Byun, Cham Han Lee, Jun Ha Hwang, A. Rum Kim, Sung Ah Moon, Mi Kyung Sung, Jung Rae Roh, Eun Sook Hwang, Jeong-Ho Hong

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Obesity causes several metabolic diseases, including diabetes. Adipogenic differentiation is an important event for fat formation in obesity. Natural compounds that inhibit adipogenic differentiation are frequently screened to develop therapeutic drugs for treating obesity. Here we investigated the effects of phorbaketal A, a natural marine compound, on adipogenic differentiation of mesenchymal stem cells. Phorbaketal A significantly inhibited adipogenic differentiation as indicated by less fat droplets and decreased expression of adipogenic marker genes. The expression of TAZ (transcriptional coactivator with PDZ-binding motif), an inhibitor of adipogenic differentiation, significantly increased during adipogenic differentiation in the presence of phorbaketal A. Phorbaketal A increased the interaction of TAZ and PPARγ to suppress PPARγ (peroxisome proliferator-activated receptor γ) target gene expression. TAZ-depleted cells showed higher adipogenic potential than that of control cells even in the presence of phorbaketal A. During cellular signaling induced by phorbaketal A, ERK (extracellular signal-regulated kinase) played an important role in adipogenic suppression; an inhibitor of ERK blocked phorbaketal A-induced adipogenic suppression. Thus, the results show that phorbaketal A inhibits adipocyte differentiation through TAZ.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalEuropean Journal of Pharmacology
Volume718
Issue number1-3
DOIs
Publication statusPublished - 2013 Sep 26

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Keywords

  • Adipogenesis
  • ERK
  • Phorbaketal A
  • PPARγ
  • TAZ

ASJC Scopus subject areas

  • Pharmacology

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