The Role of Creb in Adipogenesis through Mammalian Target of Rapamycin of Complex 1 (mTORC1) Pathyway

Abstract

One of the tissues taking the biggest part in the pathogenesis of obesity is adipose tissue mainly formed by white fat cells. Recently, the processes adipogenesis become a treatment target for obesity. One of the pathway that allegedly participated in the process of adipogenesis is activated via CREB. The upstream pathway is by means of protein of mammalian targets of rapamycin (mTOR). This study was aimed to determine the role of CREB in adipogenesis through the activation of p70S6K1 by mTORC1. This was an experimental study. Subjects were primary cultured preadipocytes taken from visceral fat of white rats (Rattus norvegicus). Cell cultures were classified into 4 groups: (K) Control of adipogenesis: without rapamycin and RNAi CREB, (A): was given rapamycin 10 nM, (B): was given RNAi CREB 100 nM, (C): was given rapamycin 10 nM and RNAi CREB 100 nM. p70S6K1, CREB activation, and expression of C/EBPδ measured on day 2, 4, and 6, and the morphology of adipocytes on day 6. Data were analyzed with Anova test, LSD test, and Pearson correlation test with 95% confidence level. The data showed that rapamycin activated p70S6K1 and caused lower CREB compared with control group during adipogenesis. These results indicated that adipogenesis was blocked, which resulted from the inhibition of p70S6K1 and CREB activation by rapamycin and RNAi CREB. The inhibition was stronger in rapamycin + RNAi CREB group. Statistically, there was significant correlation between p70S6K1 and CREB; and between CREB and C/EBPδ. It was concluded that the role of CREB in adipogenesis was mediated by the activation of p706K1 by mTORC1.