Fatty acids as signal transducing molecules: involvement in the differentiation of preadipose to adipose cells.

Fatty acids are important metabolic substrates for adipose tissue and act, in preadipose cells, as potent inducers of various proteins directly involved in their metabolism. We have investigated the long-term effects of fatty acids on the conversion process of preadipose Ob1771 cells to adipose cells. Chronic exposure of cells to palmitate led, in a dose-dependent manner, to a strong stimulation of cell differentiation; this effect was confined to terminal events whereas fatty acids did not affect expression of early genes related to commitment of adipoblasts to preadipose cells. Adipogenic action of fatty acids did not require their metabolism as 2-bromopalmitate, which is not metabolized by preadipose cells, was more effective than palmitate in inducing differentiation. The critical role of fatty acids occurred during the first 3 days of the differentiation process and led subsequently to an increase in the number of differentiated cells by means of enhancement of post-confluent mitoses and over-expression of terminal differentiation-related genes. These results thus provide, at the molecular level, a potential link observed in vivo between an increase in fatty acid supply induced by high-fat or high-carbohydrate diets and the hyperplastic development of adipose tissue.