Molecular Mechanism of Stem Cell Differentiation into Adipocytes and Adipocyte Differentiation of Malignant Tumor

Figure 3

Regulation of adipocyte differentiation. A regulatory loop exists between PPARγ and CEBP activation. Transcription factor Coe (EBF) activates CEBPα, CEBPα activates EBF1, and EBF1 activates PPARγ. CEBPβ and CEBPδ act directly on the PPARγ gene by binding its promoter and activating transcription. CEBPα, CEBPβ, and CEBPδ can activate the EBF1 gene and KLF5. The EBF1 and KLF5 proteins in turn bind the promoter of PPARγ, which becomes activated. Other hormones, such as insulin, can affect the expression of PPARγ and other transcription factors, such as SREBP1c. PPARγ can form a heterodimer with the RXRα. In the absence of activating ligands, the PPARγ-RXRα complex recruits transcription repressors, such as nuclear receptor corepressor (NCoR) 2, NCoR1, and HDAC3. Upon binding with activating ligands, PPARγ causes a rearrangement of adjacent factors. Corepressors such as NCoR2 are lost, and coactivators such as Transcription intermediary factor TIF2, CBP, and p300 are recruited, which can result in the expression of Cyclic AMP-responsive element-binding protein (CREB) followed by PPARγ. PPARγ expression initiates the expression of downstream genes, including angiopoietin-related protein PGAR, Perilipin, FABP4, CEBPα, fatty acid transport-related proteins, carbohydrate metabolism-related proteins, and energy homeostasis-related proteins.