PPARγ 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, PPARγ, although it does not activate the related receptors, PPARα, PPARδ or RARα. AS-6 interacts directly with the PPARγ 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 PPARγ with a novel chemical structure.