Sodium butyrate in combination with insulin or dexamethasone can terminally differentiate actively proliferating...

Sodium butyrate arrests the growth of actively proliferating Swiss 3T3 cells. A previous report from our laboratory describes the pattern of expression of a representative group of growth-associated genes following treatment of Swiss 3T3 cells with sodium butyrate. The results of this study suggest that sodium butyrate-induced growth arrest involves events which lead to adipocyte differentiation (Toscani, A., Soprano, D.R., and Soprano, K.J. (1988) Oncogene Res. 3, 233-238). However, while sodium butyrate by itself could apparently initiate adipogenesis, it alone was not sufficient to maintain this differentiation state. We now wish to further characterize the role of sodium butyrate in adipocyte differentiation. Subconfluent cultures of Swiss 3T3 cells were treated with sodium butyrate in combination with other agents known to induce Swiss 3T3 cell adipogenesis (e.g. 1-methyl-3-isobutylxanthine, insulin, and dexamethasone) and then analyzed at various times thereafter for: (a) the presence of high concentrations of intracellular lipid as detected by microscopic examination of treated cells following staining with lipid-specific dyes and (b) the expression of four genes known to be modulated during the differentiation of preadipocytes into mature adipocytes (actin, adipsin, lipoprotein lipase, and adipocyte P2). Our results show that sodium butyrate in combination with either insulin or dexamethasone can fully differentiate Swiss 3T3 cells into adipocytes, at least as determined by accumulation of high levels of intracellular lipid. Moreover, the sodium butyrate-mediated process of differentiation can occur in subconfluent, actively proliferating cells. Thus, these experiments describe a new, previously unidentified activity of sodium butyrate and also suggest that this model system may be a useful one to study the relationship between growth arrest and differentiation.