Differentiation of Embryonic Stem Cells as a Model to Study Gene Function During the Development of Adipose Cells

The white adipose tissue stores energy in the form of triglycerides in time of nutritional excess and releases free fatty acids during food deprivation. The adipose tissue mass is determined by the balance between energy intake and expenditure. Alterations of this steady state can lead to overweight and obesity, which is often accompanied by metabolic disorders associated with cardiovascular diseases such as hypertension and type II diabetes. The ongoing explosion in the incidence of obesity has focused attention on the development of adipose cells. Mainly, the in vitro system used to study adipogenesis is immortal preadipocyte cell lines ( 1 ). However, these systems are limited for studies of early differentiation because they represent already determined cells. The commitment of embryonic stem (ES) cells into the adipocyte lineage offers the possibility to study the first steps of adipose cell development. In addition, the combination of genetic manipulations of undifferentiated ES cells and in vitro adipocyte differentiation facilitates elucidation of the role of genes expressed during adipose cell conversion. Terminal differentiation of preadipocytesi into adipocytes is a multistep process. Several marker genes have been identified, and the hormonal regulation of these different genes has been studied in detail in recent years ( 1 ). However, the requirement for adipogenesis of genes known to be expressed during the different stages of differentiation remains to be investigated (Fig. 1 ).

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