Genetic and epigenetic transgenerational implications related to omega-3 fatty acids. Part I: maternal FADS2 genotype and DNA methylation correlate with polyunsaturated fatty acid status in toddlers: an exploratory analysis

Lupu, Daniel S.; Cheatham, Carol L.; Corbin, Karen D.; Niculescu, Mihai D.

doi:10.1016/j.nutres.2015.09.004

Cited by 22 publications

(9 citation statements)

References 25 publications

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“…It appears that the combined genetic and nutritional effects of parents on offspring growth resulted in higher growth of fish obtained from high fads2 expression and parents fed diet F. Growth was higher in high fads2 than low fads2 groups regardless of parental diet intake. Studies in humans showed that LC-PUFA metabolism in babies could be affected by maternal FADS2 genetic and epigenetic status [43].…”

Section: Discussionmentioning

confidence: 99%

Effects of Dietary Lipid Composition and Fatty Acid Desaturase 2 Expression in Broodstock Gilthead Sea Bream on Lipid Metabolism-Related Genes and Methylation of the fads2 Gene Promoter in Their Offspring

Türkmen

Perera

Zamorano

et al. 2019

IJMS

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Polyunsaturated fatty acids (PUFA) in parental diets play a key role in regulating n-3 LC-PUFA metabolism of the offspring. However, it is not clear whether this metabolic regulation is driven by the precursors presented in the diet or by the parental ability to synthesize them. To elucidate this, broodstocks of gilthead sea bream with different blood expression levels of fads2, which encodes for the rate-limiting enzyme in the n-3 LC-PUFA synthesis pathway, were fed either a diet supplemented with alpha-linolenic acid (ALA, 18:3n-3) or a control diet. The progenies obtained from these four experimental groups were then challenged with a low LC-PUFA diet at the juvenile stage. Results showed that the offspring from parents with high fads2 expression presented higher growth and improved utilization of low n-3 LC-PUFA diets compared to the offspring from parents with low fads2 expression. Besides, an ALA-rich diet during the gametogenesis caused negative effects on the growth of the offspring. The epigenetic analysis demonstrated that methylation in the promoter of fads2 of the offspring was correlated with the parental fads2 expression levels and type of the broodstock diet.Int. J. Mol. Sci. 2019, 20, 6250 2 of 20 FM and FO in fish feeds [7,8]. Complete substitution of FO by VO adversely affects fish immune system and stress and disease resistance [3][4][5][6]. In addition, it also reduces the muscle content of long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFA), such as EPA (20:5n-3) and DHA (22:6n-3) that negatively affect the nutritional value of farmed fish for humans [4,[9][10][11][12].Most fish cannot synthesize n-3 and n-6 PUFA de novo and they must be supplied in the diet. Generally, essential fatty acid (EFA) requirements of freshwater fish can be met by the supply of 18:3n-3 and 18:2n-6 fatty acids in their diets, whereas the EFA requirement of marine fish can only be met by supplying the LC-PUFA, EPA, and DHA [13]. Unlike freshwater fish, marine fish either lack or show a low activity of ∆6-desaturase, and thus require the long chain PUFA's, EPA, and DHA to meet their EFA requirement. The bioconversion of 18:3n-3 to EPA and DHA involves desaturations at ∆-6 and ∆-5 positions in the carbon backbone and an intermediate 2-carbon chain elongation step. Synthesis of DHA from EPA requires elongation of EPA to 22:5n-3 and 24:5n-3 which is then converted to 24:5n-3 and 24:6n-3 by ∆6-desaturase and finally shortened to DHA by β-oxidation. Among enzymes involved in n-3 LC-PUFA synthesis, ∆-6-desaturase enzyme (Fads2), encoded by fads2 gene, is considered to be the rate-limiting step in the biosynthetic pathway of PUFA in gilthead sea bream [14,15]. LC-PUFA synthesis also involves chain elongation catalyzed by elongases (Elovl) with different substrate preferences [16]. Among them Elovl6 is a key lipogenic enzyme that elongates long-chain saturated and monounsaturated fatty acids of 12, 14, and 16C, and has received much attention due to its link with certain metabolic disorders [17]. LC-PUFA may have a direc...

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Section: Discussionmentioning

confidence: 99%

Effects of Dietary Lipid Composition and Fatty Acid Desaturase 2 Expression in Broodstock Gilthead Sea Bream on Lipid Metabolism-Related Genes and Methylation of the fads2 Gene Promoter in Their Offspring

Türkmen

Perera

Zamorano

et al. 2019

IJMS

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“…Additionally, the methylation status of CpG sites in two critical regulatory regions of the FADS cluster have been shown to be associated with blood and tissue PUFA levels as well as an important phenotype (e.g. immediate and intermediate memory) in toddlers [ 43 , 44 ]. It is clear that further investigation is needed to tease out the importance of the methylation status of CpG sites in this important FADS regulatory region.…”

Section: Discussionmentioning

confidence: 99%

Uncovering the DNA methylation landscape in key regulatory regions within the FADS cluster

Rahbar¹,

Ainsworth²,

Howard³

et al. 2017

PLoS ONE

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Genetic variants near and within the fatty acid desaturase (FADS) cluster are associated with polyunsaturated fatty acid (PUFA) biosynthesis, levels of several disease biomarkers and risk of human disease. However, determining the functional mechanisms by which these genetic variants impact PUFA levels remains a challenge. Utilizing an Illumina 450K array, we previously reported strong allele-specific methylation (ASM) associations (p = 2.69×10−29) between a single nucleotide polymorphism (SNP) rs174537 and DNA methylation of CpG sites located in the putative enhancer region between FADS1 and FADS2, in human liver tissue. However, this array only featured 20 CpG sites within this 12kb region. To better understand the methylation landscape within this region, we conducted bisulfite sequencing of the region between FADS1 and FADS2. Liver tissues from 50 male subjects (27 European Americans, 23 African Americans) were obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, and used to ascertain the genotype at rs174537 and methylation status across the region of interest. Associations between rs174537 genotype and methylation status of 136 CpG sites were determined. Age-adjusted linear regressions were used to assess ASM associations with rs174537 genotype. The majority of CpG sites (117 out of 136, 86%) exhibited high levels of methylation with the greatest variability observed at three key regulatory regions–the promoter regions for FADS1 and FADS2 and a putative enhancer site between the two genes. Eight CpG sites within the putative enhancer region displayed significant (FDR p <0.05) ASM associations with rs174537. These data support the concept that both genetic and epigenetic factors regulate PUFA biosynthesis, and raise fundamental questions as to how genetic variants such as rs174537 impact DNA methylation in distant regulatory regions, and ultimately the capacity of tissues to synthesize PUFAs.

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“…In mice, methylation of the CpG island at the promoter region of Fads2 negatively correlates with the expression of the gene [43], though it appears that the human FADS2 expression can also be regulated by methylation at four distal CpG sites in a non-CpG island region [44] or by methylation at a CpG island that extends to the beginning of the first intron [63]. In the case of gilthead sea bream, the analyzed CpG sites (-331 to -87) within a CpG island at the proximal promoter region appear highly refractory to programing with ALA, but we cannot totally exclude that other, more distal CpG sites, would be susceptible to nutritional programming.…”

Section: Constrains To Program Fish Fads2mentioning

confidence: 99%

Stearoyl-CoA desaturase (scd1a) is epigenetically regulated by broodstock nutrition in gilthead sea bream (Sparus aurata)

et al. 2019

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Genetic and epigenetic transgenerational implications related to omega-3 fatty acids. Part I: maternal FADS2 genotype and DNA methylation correlate with polyunsaturated fatty acid status in toddlers: an exploratory analysis

Cited by 22 publications

References 25 publications

Effects of Dietary Lipid Composition and Fatty Acid Desaturase 2 Expression in Broodstock Gilthead Sea Bream on Lipid Metabolism-Related Genes and Methylation of the fads2 Gene Promoter in Their Offspring

Effects of Dietary Lipid Composition and Fatty Acid Desaturase 2 Expression in Broodstock Gilthead Sea Bream on Lipid Metabolism-Related Genes and Methylation of the fads2 Gene Promoter in Their Offspring

Uncovering the DNA methylation landscape in key regulatory regions within the FADS cluster

Stearoyl-CoA desaturase (scd1a) is epigenetically regulated by broodstock nutrition in gilthead sea bream (Sparus aurata)

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