|Waterland, Robert - Rob|
Submitted to: Scandinavian Journal of Food & Nutrition
Publication Type: Review Article
Publication Acceptance Date: 2/20/2006
Publication Date: 3/7/2006
Citation: Waterland, R.A., Rached, M. 2006. Developmental establishment of epigenotype: a role for dietary fatty acids? Scandinavian Journal of Food & Nutrition. 50(S2):21-26. Interpretive Summary:
Technical Abstract: Human epidemiologic data indicate that nutrition during prenatal and early postnatal development can affect susceptibility to various chronic diseases in adulthood (the developmental origins hypothesis). Controlled studies in animal models corroborate that nutritional exposures during critical periods of development wield lasting influences on gene expression and metabolism, but our understanding of the fundamental biological mechanisms underlying such phenomena remains rudimentary. Nutritional influences on the developmental establishment of epigenetic gene regulatory mechanisms could link early nutrition to adult chronic disease susceptibility. Just as genetic variation contributes to individual susceptibility to chronic disease, it is increasingly evident that so too does epigenetic variation. Very little is known about the factors that contribute to interindividual variation in epigenotype. It is critically important to determine whether nutrition and other environmental influences during development affect the establishment of human epigenotype. Most previous studies of nutritional influences on epigenetic regulation have focused on nutrients known to affect one-carbon metabolism. For example, supplementation during development with methyl donors including folic acid and vitamin B12 appears to induce DNA hypermethylation at specific loci by increasing the flux through the DNA methylation pathway. This article will consider the mechanisms by which fatty acid nutrition during prenatal and early postnatal nutrition might affect the establishment of epigenetic gene regulatory mechanisms. Choline, a component of the phospholipid phosphatidylcholine, stands at the intersection of lipid and one-carbon metabolism; upon conversion to betaine, its three methyl groups are available to one-carbon metabolism. Potentially much more important than providing methyl groups for DNA methylation, dietary fatty acids could affect the establishment of epigenetic mechanisms by stimulating transcription of specific genes during critical developmental windows. For example, the peroxisome proliferator activated receptor-alpha (PPAR-alpha) transcription factor is activated by a variety of fatty acids to transactivate specific genes. PPAR-alpha-mediated transcriptional activation during critical ontogenic periods could impede epigenetic silencing of genes involved in fatty acid metabolism. Lastly, recent data indicate that lipids and lipoprotein components interact directly with chromatin structure to influence gene expression. Hence, intake of specific dietary fatty acids during development could induce persistent changes in gene expression by altering the establishment of epigenetic mechanisms.