When preadipose 3T3 cells arrest their growth and interact with an external adipogenic factor, they begin to convert to adipose cells. This is a faithful model of the formation of adipose cells in early developement. In the process of adipose conversion there is an extensive revision of the protein composition of the cytoplasm; this is necessary in order to provide the lipogenic and lipolytic enzymes and accesssory proteins for performance of the differentiated functions of the cell type. Using cDNA clones and ultimately genomic clones for some of the proteins participating in the differentiation, we will study the integrated or programmatic aspects of the adipose conversion, in order to learn how the cell coordinates the expression of this group of genes. Studies of transcription and mRNA formation in preadipose 3T3 cells, in converted 3T3 adipose cells and in cells of another 3T3 line unable to undergo conversion in response to adipogenic factor will enable us to define the order in which the genes respond. In particular, we will perform a kinetic analysis of these events during the course of adipose conversion. The relation of the order of expression of these genes to changes in chromatin structure will be explored. The expression of these genes will be studied in other tissues, such as liver and brain, whose program of differentiation overlaps the program in adipose differentiation. In this way we hope to learn how the expression of a given gene can be integrated into different programs in different cell types. These studies permit an approach to the study of obesity using cultured cells. Analysis of the molecular and cellular changes necessary for the formation of adipose cells from their precursors may be expected to shed light on the genesis of hyperplastic obesity.
