Figure 4

Schematic overview of the pathway controlling translational changes in adipogenesis. The PI3K/AKT/mTORC1 pathway, which is stimulated by insulin, leads to activation of eIF4B, which changes preferences in translation activity [38]. Regulation of C/EBPα could possibly be explained by up-regulation of eIF4b activity, as members of the C/EBP family are regulated at the translational level (dashed line). Additionally an increase in translation of adipogenesis genes mediated by eIF4B is thinkable (dashed line). c-MYC over-expression in cycling cells has been reported to block exit from the cell cycle, accelerate cell division, and increase cell size (reviewed in [45]). When c-MYC levels are high, 3T3-L1 adipoblasts are locked in a proliferation-competent state and normal differentiation can not be activated. Persisting high levels of c-MYC can inhibit the expression of genes that promote adipogenesis namely C/EBPα and PPARγ2 and therefore prevent terminal differentiation of preadipocytes to mature adipocytes [46, 47]. c-MYC is an important regulator of ribogenesis, as it activates Pol I, Pol II and Pol III [49]. As a supplement in media, Ghrelin promotes the proliferation and differentiation of 3T3-L1 preadipocytes by increasing the mRNA levels of PPARγ and C/EBPα [52]. Ghrelin mRNA over-expressing 3T3-L1 cells, on the other hand, demonstrated significantly attenuated differentiation of preadipocytes into adipocytes [53]. Down-regulation of Ghrelin levels in the early phase of adipogenesis fits the known facts indicating a role of decreased endogenous Ghrelin levels in promoting adipogenesis).