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The aim was to perform an in-depth characterization of pteryxin in the anti-obesity related molecular mechanisms using 3T3-L1 preadipocytes. Cells were treated with pteryxin 20 (PTX20) or 50 (PTX50) μg/mL during cell differentiation or maintenance period. Pteryxin dose-dependently suppressed adipogenic gene network. PTX20 downregulated key lipogenic genes suppressing fatty acid synthesis allotting the anti-adipogenesis in the late adipocyte formation stage. PTX50 downregulated adipogenesis related genes, and accelerated lipolytic activity by repressing the adipocyte size marker gene, MEST. In addition to Wnt5a, PTX50 suppressed adipocyte differentiation through TGF-β/Smad3 signaling pathway with the maximum adiposity inhibition in the early stage of adipogenesis and regulated the carbohydrate metabolism. Pteryxin regulated phosphorylation of ERK1/2 and AMPK, and decreased p38 MAPK to repress the mature adipocyte formation. Overall, we have demonstrated the anti-adipogenic characteristics of pteryxin consistent to its dose. PTX50 may serve as a potential candidate to ameliorate adiposity and improve the carbohydrate metabolism.

Several types of coumarins have been isolated from Peucedanum japonicum Thunb (PJT) and we previously reported the anti-obesity activity of pteryxin (PTX), as an active compound of PJT. However, during our research, we identified another variety of PJT, which does not contain any PTX. Here, we prepared concentrates from the two varieties of PJT and demonstrated that dietary PJT concentrates both with and without PTX significantly decreased the relative weights of white adipose tissue (WAT) and mRNA levels of lipogenic genes in epididymal WAT. Furthermore, we compared the inhibitory effects of dihydropyranocoumarins of PJT on lipid accumulation of differentiated 3T3-L1 adipocytes. All of the dihydropyranocoumarins used in this study significantly inhibited lipid accumulation and lipogenic-related gene expressions in 3T3-L1 adipocytes. However, the magnitudes of the effects were distinctly different. The present study demonstrated that several dihydropyranocoumarins in PJT possess anti-obesity activities, which mainly act by inhibiting lipogenesis in adipocytes.