Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial.

Background & Aims: Genetic variation in both patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain.

Methods: One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15-18months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography.

Fat and carbohydrate intake over three generations modify growth, metabolism and cardiovascular phenotype in female mice in an age-related manner.

Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing.

Supplementation with N-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells.

Background: Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans.

Methods And Results: We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years).

DNA methylation, ageing and the influence of early life nutrition.

It is well established that genotype plays an important role in the ageing process. However, recent studies have suggested that epigenetic mechanisms may also influence the onset of ageing-associated diseases and longevity. Epigenetics is defined as processes that induce heritable changes in gene expression without a change in the DNA nucleotide sequence.

Effect of sex hormones on n-3 polyunsaturated fatty acid biosynthesis in HepG2 cells and in human primary hepatocytes.

Female humans and rodents have been shown to have higher 22:6n-3 status and synthesis than males. It is unclear which sex hormone is involved. We investigated the specificity of the effects of physiological concentrations of sex hormones in vitro on the mRNA expression of genes involved in polyunsaturated fatty acid (PUFA) biosynthesis and on the conversion of [d5]-18:3n-3 to longer chain fatty acids.

Maternal fat intake in rats alters 20:4n-6 and 22:6n-3 status and the epigenetic regulation of Fads2 in offspring liver.

Poor prenatal nutrition, acting through epigenetic processes, induces persistent changes in offspring phenotype. We investigated the effect of maternal fat intake on polyunsaturated fatty acid (PUFA) status and on the epigenetic regulation of Fads2, encoding Δ6 desaturase (rate limiting in PUFA synthesis), in the adult offspring. Rats (n=6 per dietary group) were fed either 3.

Epigenetics: are there implications for personalised nutrition?

Purpose Of Review: This review critically evaluates recent advances in understanding the role of epigenetics in nutrition. Findings from animal models and human cohorts are discussed in the context of whether or not epigenetics may be an important factor in the progress towards the goal of personalised nutrition.

Recent Findings: Maternal dietary fat, folic acid, protein and total energy intakes induce altered epigenetic regulation of specific genes in the offspring which are associated with altered tissue function.

Vascular dysfunction induced in offspring by maternal dietary fat involves altered arterial polyunsaturated fatty acid biosynthesis.

Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w) or 21%(w/w) fat enriched in either 18:2n-6, trans fatty acids, saturated fatty acids, or fish oil.

Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition.

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge.

Increasing the folic acid content of maternal or post-weaning diets induces differential changes in phosphoenolpyruvate carboxykinase mRNA expression and promoter methylation in rats.

Environmental exposures throughout the life course, including nutrition, may induce phenotypic and epigenetic changes. There is limited information about how timing affects the nature of such effects induced by a specific nutritional exposure. We investigated the effect of increased exposure to folic acid before birth or during the juvenile-pubertal period in rats on the epigenetic regulation of glucose homeostasis.

Dietary protein restriction during F0 pregnancy in rats induces transgenerational changes in the hepatic transcriptome in female offspring.

There is considerable evidence for non-genomic transmission between generations of phenotypes induced by environmental exposures during development, although the mechanism is poorly understood. We investigated whether alterations in expression of the liver transcriptome induced in F1 offspring by feeding F0 dams a protein-restricted (PR) diet during pregnancy were passed with or without further change to two subsequent generations. The number of genes that differed between adult female offspring of F0 protein-restricted (PR) and protein-sufficient (PS) dams was F1 1,684 genes, F2 1,680 and F3 2,062.

Effect of sex and dietary fat intake on the fatty acid composition of phospholipids and triacylglycerol in rat heart.

Variations in the fatty acid composition of lipids in the heart alter its function and susceptibility to ischaemic injury. We investigated the effect of sex and dietary fat intake on the fatty acid composition of phospholipids and triacylglycerol in rat heart. Rats were fed either 40 or 100g/kg fat (9:1 lard:soybean oil) from weaning until day 105.