CONICET | Buscador de Institutos y Recursos Humanos

Adipogenesis comprises the signaling program of cell differentiation by which preadipocytes become adipocytesand is a key process that is required in adipocyte hypertrophy in the development of obesity. In this study, weinvestigated the effect of 11,13 dihydro-[11R]-dehydroleucodine (i.e., leucodine), a sesquiterpene lactone obtainedfrom the reduction of dehydroleucodine, on adipogenesis of 3T3-L1 preadipocyte. 11,13 dihydro-[11R]-dehydroleucodine blocked the accumulation of lipid droplets stained with Oil Red O and inhibited the increaseof triglycerides in the adipocytes (IC50: 71.0 ± 4.1 μM). Expressions of Glut-4, adiponectin and perilipin-2 wereblocked in the presence of 11,13 dihydro-[11R]-dehydroleucodine. Furthermore, expression of PPARγ and C/EBPα was significantly inhibited by 11,13 dihydro-[11R]-dehydroleucodine as well as the expression of C/EBPβwas also strongly inhibited in time- and concentration-dependent manner. This is consistent with the inhibitoryeffect of 11,13 dihydro-[11R]-dehydroleucodine on the early stage of adipogenesis. Thus, the proliferation ofpreadipocytes were also suppressed by addition of 11,13 dihydro-[11R]-dehydroleucodine during the first 48 hafter induction. These results indicate that 11,13 dihydro-[11R]-dehydroleucodine may selectively affect mitoticclonal expansion to block preadipocyte differentiation. 11,13 dihydro-[11R]-dehydroleucodine stopped the cellcycle at the G0/G1 phase by diminishing the increase of phosphorylation of Rb, Erk1/2 and Akt while increasingthe expression of p27. Collectively, our results indicate that the inhibition of early stage preadipocytes differentiationby 11,13 dihydro-[11R]-dehydroleucodine may be associated with cell cycle arrest at the G0/G1 phasethrough upregulation of p27 expression.