DNA Methylation Pattern in Overweight Women under an Energy-Restricted Diet Supplemented with Fish Oil

Abstract

Dietary factors modulate gene expression and are able to alter epigenetic signatures in peripheral blood mononuclear cells (PBMC). However, there are limited studies about the effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on the epigenetic mechanisms that regulate gene expression. This research investigates the effects of n-3-rich fish oil supplementation on DNA methylation profile of several genes whose expression has been reported to be downregulated by n-3 PUFA in PBMC: CD36, FFAR3, CD14, PDK4, and FADS1. Young overweight women were supplemented with fish oil or control in a randomized 8-week intervention trial following a balanced diet with 30% energy restriction. Fatty acid receptor CD36 decreased DNA methylation at CpG +477 due to energy restriction. Hypocaloric diet-induced weight loss also reduced the methylation percentages of CpG sites located in CD14, PDK4, and FADS1. The methylation patterns of these genes were only slightly affected by the fish oil supplementation, being the most relevant to the attenuation of the weight loss-induced decrease in CD36 methylation after adjusting by baseline body weight. These results suggest that the n-3 PUFA-induced changes in the expression of these genes in PBMC are not mediated by DNA methylation, although other epigenetic mechanisms cannot be discarded.

Genome-wide identification of mononuclear cell DNA methylation sites potentially affected by fish oil supplementation in young infants: A pilot study

“…Our findings are somewhat in contrast with other studies showing that n-3 LCPUFA intake is associated with gene methylation changes [6,30,31] in humans, although these studies differ in the timing of intervention (gestational versus postnatal) and also did not address potential confounding from cell heterogeneity in the samples. Furthermore, differences in control supplement might also explain some of the discrepancy between results, as our study provided n-6 PUFA, which is different from other studies [6,30].…”

“…Furthermore, differences in control supplement might also explain some of the discrepancy between results, as our study provided n-6 PUFA, which is different from other studies [6,30]. However, as this is a pilot study, we interpret these results more as an indication of which possible epigenome changes due to n-3 LCPUFA supplementation could occur and acknowledged the limited power of the study.…”

Efecto de los ácidos grasos poliinsaturados en la prevención de la obesidad a través de modificaciones epigenéticas

“…Además, este estudio indica que la interacción materna con ALA durante la gestación y lactancia podría alterar diferencialmente el metabolismo de n-3 y n-6 74 . En humanos, un estudio reciente realizado en mujeres jóvenes con sobrepeso y tratadas mediante una dieta calórico-restrictiva ha demostrado que la suplementación de n-3 derivados del aceite de pescado (>1.300 mg/día en forma de 6 cápsulas diarias) induce pequeños cambios epigenéticos que reducen la metilación del ADN del gen CD36 de células mononucleares de la sangre, una vez ajustado por el peso corporal de las mujeres 76 .…”

DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice

“…n-3 PUFAs induce epigenetic modifications as demonstrated in leukemia cells treated with eicosapentaenoic acid (EPA) [15,16]. However, studies on PUFAs in human or rodent models are scarce [17,18,19,20,21]. Methylation changes may be gene specific as observed for fatty acid desaturases (FADS).…”

“…FADS2 encodes delta-6-desaturase, whereas FADS1 encodes delta-5-desaturase [17]. When adult humans are supplemented with fish oil, changes in the methylation promoter of FADS2 [17], but not FADS1 [17,18], in peripheral blood mononuclear cells are found. A similar response was observed in animals [19,20].…”