Polyunsaturated fatty acids play a critical role in the structure and function of the developing nervous system. It has been proposed that fatty acids may effect a variety of biologic processes through the activation of the peroxisome proliferator activated receptors (PPARs)-ligand activated transcription factors. In this report, we demonstrate that fatty acids can inhibit the proliferation of the human neuronal cell line IMR-32. The fatty acids linoleate, alpha-linoleate, arachidonate, docosahexaenoate, and oleate all inhibited [(3)H]thymidine incorporation of IMR-32 cells after 72 h. Fatty acid supplementation also led to the morphologic differentiation of the IMR-32 cells. Linoleate and arachidonate, fatty acids of the n-6 series, induced the most extensive differentiation. Furthermore, the addition of fatty acids to IMR-32 cells led to PPAR activation, suggesting that PPAR activation may be an important event in fatty acid modulation of IMR-32 cell growth. In support of this hypothesis, clofibric acid, a specific ligand of PPARalpha, also inhibited IMR-32 cell proliferation and strongly induced PPAR activation. Together these results suggest that fatty acids may play an important role in the development of neuronal precursor cells and that activation of the PPARs may be one pathway by which fatty acids modulate the growth and differentiation of neuronal precursor cells.
Copyright 2000 Wiley-Liss, Inc.