Regulating Adipogenesis

Abstract

The raison d’etre of the adipocyte is to store energy (in the form of triacylglycerol) for use during periods of caloric insufficiency. Adipocytes first appear late in fetal development preparatory to postnatal life when a substantial energy reserve is needed to survive periods of fasting. Considerable progress has been made during the past few years in our understanding of the adipocyte differentiation program. This review will focus on the roles of the CAAT/enhancer binding protein (C/EBP) and peroxisome proliferator-activated receptor (PPAR) families of transcription factors in the differentiation program. The reader is referred to other recent reviews (1–3) for references too numerous to include in this Minireview. Our understanding of adipocyte differentiation derives largely from studies with preadipose cell lines in culture, notably the C3H10T1/2 and NIH 3T3 fibroblastic cell lines and the 3T3-L1 and 3T3-F442A preadipocyte lines (1). Treatment of multipotent C3H10T1/2 cells with 5-azacytidine gives rise to cells committed to the myogenic, adipogenic, or chondrogenic lineages. This is consistent with the view that the adipose lineage arises from the same multipotent stem cell population of mesodermal origin that gives rise to the muscle and cartilage lineages (1). When appropriately induced with hormonal agents (e.g. glucocorticoid, insulin-like growth factor-1, and cyclic AMP or factors that mimic these agents) committed preadipocytes differentiate into adipocytes in culture. A large body of evidence shows that differentiation of 3T3 preadipocytes faithfully mimics the in vivo process giving rise to cells that possess virtually all of the biochemical and morphological characteristics of adipocytes (2). Following hormonal induction, confluent preadipocytes undergo mitotic clonal expansion, become growth arrested, and then coordinately express adipocyte gene products (1). Several transcription factors have been identified, which act cooperatively and sequentially to trigger the terminal differentiation program (3–5). These include members of the C/EBP and PPAR families. The sequence of expression of certain of these transcription factors during differentiation is outlined in Fig. 1. It should be noted that these patterns differ somewhat depending upon the differentiation protocol and preadipocyte cell line employed, e.g. 3T3-L1 versus 3T3-F442A versus NIH 3T3 cells.