Fatty acids and epigenetics

Purpose of review The purpose of this review is to assess the findings of recent studies on the effects of fatty acids on epigenetic process and the role of epigenetics in regulating fatty acid metabolism. Recent findings The DNA methylation status of the Fads2 promoter was increased in the liver of the offspring of mice fed an alpha linolenic acid enriched diet during pregnancy. In rats, increasing total maternal fat intake during pregnancy and lactation induced persistent hypermethylation of the Fads2 promoter in the liver and aortae of their offspring. However, increased fish oil intake in adult rats induced transient, reversible hypermethylation of Fads2. High fat feeding in rodents also altered the levels of histone methylation in placentae and in adipose tissue. Dietary docosahexaenoic acid supplementation in pregnant women induced marginal changes in global DNA methylation in cord blood leukocytes. A high fat diet altered the DNA methylation status of specific genes in skeletal muscle in young men. Summary
There are emerging findings that support the suggestion that fatty acids, in particular polyunsaturated fatty acids, can modify the epigenome. However, there is a need for rigorous investigations that assess directly the effect epigenetic modifications induced by fatty acids on gene function and metabolism. (Authors abstract)

Nutrigenomics is now a well established area of research in nutritional science. Polymorphisms have been identified in genes involved in a wide range of pathways that alter nutrient metabolism and modify disease risk. Epigenetic marks can exhibit plasticity throughout the life course, albeit to varying degrees, and can be modified by environmental factors including diet. This suggests that while variations in the epigenetic control of genes involved in nutrient metabolism may contribute to differences between individuals in their nutrient requirements and susceptibility to disease, nutritional interventions or dietary choices may modify the epigenome. One implication of this bidirectional interaction between the diet and the epigenome is that it may be possible to reprogramme epigenetic marks that are associated with increased disease risk by nutritional or lifestyle interventions. The induction and maintenance of epigenetic marks, in particular DNA methylation and some covalent modifications of histones, are associated intimately with 1 carbon metabolism, and hence there is a substantial body of evidence, which shows that dietary intakes of nutrients involved in this pathway alter the epigenetic regulation of genes.  The purpose of this review is to discuss the recent studies that have investigated the interaction between fatty acids and the epigenome and to consider the implications of the findings for human health.

The author notes key points including, altered maternal fat intake during pregnancy and lactation can induce persistent changes in the epigenetic regulation by DNA methylation and histone modifications of genes in the tissues of the offspring; altered dietary fat in adults can induce altered epigenetic regulation of specific genes, although this may be transient and reversible and induced changes in the epigenetic regulation of genes by dietary fatty acid intake is potentially an important mechanism in metabolic control and in disease risk, but there is a substantial need for studies that demonstrate a direct effect of epigenetic changes on transcription and metabolism. Recent studies of the interaction between fatty acids and the epigenome encompass two general areas of research: the effect of maternal fatty acid intake on the epigenome of the offspring and the effect of manipulating the adult diet and on epigenetic outcomes.  It is not known at present how dietary fatty acids modify the epigenome. Short chain fatty acids can inhibit histone deactylase activity. Variation in energy intake leading to changes in cellular NADþ per NADH may alter histone acetylation by modulating the activities of the histone deaceylases; sirtuins. It is possible that these processes may contribute to epigenetic changes induced by high fat feeding, but cannot explain the effects on individual fatty acid species on epigenetic marks. There are emerging findings that support the idea that dietary fatty acids can modify the epigenome.  However, the specificity of such effects is not clear due, in part, to the limited characterization of the diets used in a number of studies. Progress in this area is also limited by the lack of experiments to show whether differential epigenetic changes that are induced by dietary fatty acids change gene function.  (Editors comments)