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PPARgamma activation and adipocyte differentiation induced by AS-6, a prenyl-phenol antidiabetic antibiotic.

Abstract
The prenyl-phenol antibiotics ascochlorin-related compounds, are known to reduce serum cholesterol and triglyceride, suppress hypertension, and ameliorate types-I and II diabetes. However, little is known about the molecular mechanism for these physiological effects. Here we report that the ascochlorin derivative, 4-O-carboxymethyl ascochlorin (AS-6) acts as a potent activator of the nuclear hormone receptor, PPARgamma, although it does not activate the related receptors, PPARalpha, PPARdelta or RARalpha. AS-6 interacts directly with the PPARgamma molecule in vitro, and induces differentiation of the mouse preadipocyte cell line 3T3-L1. Our results suggest that AS-6 is a partial agonist for PPARgamma with a novel chemical structure.
AuthorsMarie Togashi, Hiromi Masuda, Teruo Kawada, Masao Tanaka, Kaname Saida, Kunio Ando, Gakuzo Tamura, Junji Magae
JournalThe Journal of antibiotics (J Antibiot (Tokyo)) Vol. 55 Issue 4 Pg. 417-22 (Apr 2002) ISSN: 0021-8820 [Print] England
PMID12061550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glycolates
  • Hypoglycemic Agents
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • 4-O-carboxymethylascochlorin
Topics
  • Adipocytes (cytology, drug effects, metabolism)
  • Animals
  • Cell Differentiation (drug effects, physiology)
  • Cell Line
  • Glycolates (pharmacology)
  • Humans
  • Hypoglycemic Agents (pharmacology)
  • Mice
  • Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
  • Transcription Factors (genetics, metabolism)
  • Transfection
  • Tumor Cells, Cultured

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