Development of a Ligand Screening Tool Using Full-Length Human Peroxisome Proliferator-Activated Receptor-Expressing Cell Lines to Ameliorate Metabolic Syndrome.

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily and include three subtypes (PPARα, PPARδ, and PPARγ). They regulate gene expression in a ligand-dependent manner. PPARα plays an important role in lipid metabolism. PPARγ is involved in glucose metabolism and is a potential therapeutic target in Type 2 diabetes. PPARδ ligands are candidates for the treatment of metabolic disorders. Thus, the detection of PPAR ligands may facilitate the treatment of various diseases. In this study, to identify PPAR ligands, we engineered reporter cell lines that can be used to quantify PPARγ and PPARδ activity. We evaluated several known ligands using these reporter cell lines and confirmed that they are useful for PPAR ligand detection. Furthermore, we evaluated extracts of approximately 200 natural resources and found various extracts that enhance reporter gene activity. Finally, we identified a main alkaloid of the Evodia fruit, evodiamine, as a PPARγ activator using this screening tool. These results suggest that the established reporter cell lines may serve as a useful cell-based screening tool for finding PPAR ligands to ameliorate metabolic syndromes.

Unusual Fracture Behavior of Slide-Ring Gels with Movable Cross-Links.

In this study, the quasi-static fracture behavior of slide-ring gels (SR gels), in which movable cross-links can slide on polymer chains, is for the first time investigated and compared to that of conventional polymer gels with fixed cross-links (FC gels). For the usual FC gels, there is a trade-off relation between toughness (fracture energy [Formula: see text]) and stiffness (Young's modulus E): with increasing cross-linking density, the Young's modulus E increases, while fracture energy [Formula: see text] decreases. However, SR gels show an unusual fracture behavior that contradicts this trade-off relation. The fracture energy of SR gels is independent of the Young's modulus, in other words, the cross-linking density; moreover, it rises with increasing slidable range of movable cross-links on polymer chains. A new molecular model is proposed by attributing the unusual fracture properties of SR gels to the relative sliding movement between polymer chains and cross-links. Utilizing this concept, simultaneous fulfillment of high stiffness and high toughness in polymer gels can be realized.