Adipose Development: From Stem Cell to Adipocyte

Cell culture models have been developed to study commitment and subsequent differentiation of preadipocytes into adipocytes. Bone morphogenetic protein 4 commits mesenchymal stem cells to the adipose lineage. Other factors, including Wnt signaling, cell density, and cell shape, play a role in lineage commitment. Following commitment to the adipose lineage, growth-arrested preadipocytes can differentiate to adipocytes by treatment with insulin-like growth factor 1, glucocorticoid and an agent that increases cAMP level. This process is characterized by a rapid and transient increase in CCAAT/enhancer binding protein (C/EBP) beta and synchronous re-entry into the cell cycle. Acquisition of DNA-binding by C/EBPbeta occurs after the transcription factor becomes phosphorylated. The cells enter a growth-arrested state and begin terminal differentiation. C/EBPalpha, peroxisome proliferator-activated receptor gamma, and adipocyte determination, and differentiation-dependent factor 1 coordinate the expression of genes that create and maintain the adipocyte phenotype.