OPTIMAL SUPPLY OF LONG-CHAIN POLYUNSATURATED FATTY ACIDS IN INFANCY

Uauy R.

Instituto de Nutricion y Tecnologia de los Alimentos INTA U of Chile. Santiago-Chile

Essential fatty acids are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long chain polyunsaturated fatty acids (LCPUFA). Results from animal and recent human studies support the essential nature of n-3 in addition to the well-established role of n-6 fatty acids for humans, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable isotope labeled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA) but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, retinal and nervous system development. Regulation of gene expression by LCPUFAs occurs at the transcriptional level and may be mediated by nuclear transcription factors activated by fatty acids. Clinical studies have shown that dietary supplementation with marine oil or single cell oils sources of LCPUFAs results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed infants matching that of human milk-fed infants.The main findings are that light sensitivity of retinal rod photoreceptors is significantly reduced in newborns with w-3 fatty acid deficiency, that DHA significantly enhances visual acuity maturation and cognitive functions. We have recently studied the possible effect of DHA on human fetal retinal maturation using microarray fluorescent reporters to assess gene expression. Computer analysis of relative expression of 2400 genes was performed. Ratio of expression +DHA/Control was unchanged in 80% of genes, 4% of genes displayed a ratio < 0.33 and for 15 % the ratio was > 3.0 We conclude that DHA is a conditionally essential nutrient for adequate neuro- development in humans. The effect is mediated not only by the known effects on membrane biophysical properties, neurotransmitter content and the corresponding electrophysiological correlates but also by a modulating gene expression of the developing retina and brain.

(Funded by Catedra Presidencial RU-96 Chilean Scientific Council )