UNDERSTANDING ADIPOCYTE DIFFERENTIATION

The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extens ively studied using preadipocyte culture systems. Committed preadipocy tes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcript ion factors peroxisome proliferator-activated receptor-gamma (PPAR-gam ma) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyte differentiatio n. Growth and differentiation of preadipocytes is controlled by commun ication between individual cells or between cells and the extracellula r environment. Various hormones and growth factors that affect adipocy te differentiation in a positive or negative manner have been identifi ed. In addition, components involved in cell-cell or cell-matrix inter actions such as preadipocyte factor-1 and extracellular matrix protein s are also pivotal in regulating the differentiation process. Identifi cation of these molecules has yielded clues to the biochemical pathway s that ultimately result in transcriptional activation via PPAR-gamma and C/EBP. Studies on the regulation of the these transcription factor s and the mode of action of various agents that influence adipocyte di fferentiation will reveal the physiological and pathophysiological mec hanisms underlying adipose tissue development.