Grifola frondosa (Maitake) extract activates PPARδ and improves glucose intolerance in high-fat diet-induced obese mice

Grifola frondosa is a mushroom that has anti-obesity effects, but the detailed mechanism is poorly understood. In this study, we found that lipid soluble extracts derived from G. frondosa (GFE) had peroxisome proliferator-activated receptor δ (PPARδ) agonist activity, inducing the expression of PPARδ-target genes in vitro. Furthermore, administration of GFE to high-fat diet-induced obese mice lowered the total blood cholesterol levels, upregulated the expression of PPARδ-target genes in skeletal muscles and improved glucose intolerance. Additionally, analyses of C₂C₁₂ myotubes revealed that GFE restored glucose uptake, which was inhibited by sodium palmitate, to normal levels. Unexpectedly, such acceleration was not abolished by a PPARδ antagonist. These results suggest that G. frondosa is a novel functional food that may prevent life-style related diseases like obesity and diabetes, and that these beneficial effects are likely to be mediated through the activation of PPARδ and a PPARδ-independent insulin signaling pathway.