Regulation of cellular differentiation and apoptosis by fatty acids and their metabolites

We have reviewed the literature regarding the effects of fatty acids and th eir metabolites on cellular differentiation and apoptosis. Results obtained in different studies have been variable, but some generalizations can be m ade. Differentiation was increased by incubation of cells with arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), prostag landin E1 (PGE(1)), prostaglandin E2 (PGE(2)), or leukotriene D4 (LTD4). Ef fects of these agents on differentiation could be magnified with the simult aneous addition of other differentiation-inducing agents like dimethylsulfo xide or retinoic acid. AA and gamma-linolenic acid increased apoptosis whil e the effects of n-3 fatty acids (EPA and DHA) and of eicosanoids varied fr om stimulation to inhibition. These inconsistencies are attributed to the d ifferences in methods used to evaluate differentiation and apoptosis, conce ntrations of fatty acids and serum, exposure time and the cell models used. Studies using the physiological concentrations of the fatty acids and stan dardized experimental conditions need to be conducted to establish effects of fatty acids and their metabolites on these cellular processes. Published by Elsevier Science Inc. All rights reserved.