PPARgamma activation and adipocyte differentiation induced by AS-6, a prenyl-phenol antidiabetic antibiotic.
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.
Togashi
Marie
M
Department of Biotechnology, Institute of Research and Innovation, Kashiwa, Japan.
Masuda
Hiromi
H
Kawada
Teruo
T
Tanaka
Masao
M
Saida
Kaname
K
Ando
Kunio
K
Tamura
Gakuzo
G
Magae
Junji
J
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D006016:Glycolates / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D006016:Glycolates; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C043832:4-O-carboxymethylascochlorin