Influence of anatomic site and age on the replication and differentiation of rat adipocyte precursors in culture.

Using a propagating cell culture system of adipocyte precursors from 70-400-g rats, we explored the possibility that regional variations in properties of adipose tissue may reflect site-specific characteristics intrinsic to the cells, rather than extracellular influences. Initially, studies were made of the nature of the fibroblastlike cells from perirenal adipose tissue stroma. Using colony-forming techniques, it was shown that these cells were adipocyte precursors; each confluent colony that was derived from a single cell displayed differentiated adipocytes. This characteristic was evident in cells from rats of all ages and persisted during secondary culture. At all ages of rats studied, perirenal cells replicated more rapidly than epididymal precursors, e.g., for 179-g rats the population-doubling times were 19.3 +/- 0.7 vs. 25.5 +/- 1.2 h (means +/- SEM, P less than 0.03). With aging of the rats, the replication rate of their perirenal cells decreased progressively. Under clonal conditions, the colony size distribution of both perirenal and epididymal precursors revealed heterogeneity in their capacity for replication, perirenal cells showing greater proliferation. These also differentiated more extensively by morphologic and enzymatic criteria. Age and site had effects that persisted through many cell generations; however, high-fat feeding had no perpetuating influence. The dissimilar properties of perirenal as compared with epididymal precursors may reflect differences in regulation of gene expression. The data are also compatible with a later development in embryological life of perirenal tissue. We suggest that the composition of the adipocyte precursor pool is an important determinant of the growth of adipose tissue that occurs in response to a nutrient load. Interregional or interindividual variation in composition may explain regional and individual differences in fat accumulation.