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. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w) throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456) in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing

Pregnancy induces selective changes in hepatic genes involved in cell proliferation and apoptosis in mice

<p>During pregnancy the liver undergoes substantial structural and metabolic adaptations to meet the nutritional demands of the mother and fetus; however, the underlying mechanism is poorly understood. To address this, we analysed the expression of the liver transcriptome in non-pregnant and early, mid and late pregnancy mice.</p

Pregnancy Induced Changes in the Mouse Liver Transcriptome

<p>Data showing variation in blood metabolites and gene expression during pregnancy. Preliminary data for further analysis.</p

The Effect of the Amount and Timing of Folic Acid Supplementation During the Life Course on the Epigenetic Regulation of Cancer Determining Genes

<p>Mandatory Folic Acid (FA) fortification of staple foods<br>in a number of countries and periconceptional supplementation has led to increased levels of FA intake. There is ongoing controversy over the effect of FA supplementation on cancer risk, with high levels of FA (≥400ug/day) associated with an increased risk of breast cancer. FA is thought to infer cancer risk through modulation of the epigenome. Here, we investigated whether variations in FA intake<br>during adulthood induced persistent changes in the<br>expression of the tumour suppressor gene Brca1 and<br>the pluripotency gene Oct-4, which play key roles in<br>DNA repair and cellular differentiation.</p

Correction: Fat and Carbohydrate Intake over Three Generations Modify Growth, Metabolism and Cardiovascular Phenotype in Female Mice in an Age-Related Manner.

[This corrects the article DOI: 10.1371/journal.pone.0134664.]

Increasing the folic acid content of maternal or post-weaning diets induces differential changes in phospheonolypyruvate 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. Rats were fed either a folic acid-adequate (AF; 1 mg/kg feed) or a folic acid-supplemented (FS; 5 mg/kg feed) diet from conception until delivery and then an AF diet during lactation. Juvenile rats were fed either the AF or the FS diet from weaning for 28 d and then an AF diet. Liver and blood were collected after a 12 h fast between postnatal days 84 and 90. Maternal FS diet increased plasma glucose concentration significantly (P &lt; 0·05) in females, but not in males. Post-weaning FS diet decreased glucose concentration significantly in females, but increased glucose concentration in males. There were no effects of the FS diet on phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in males, while the pattern of expression was related to plasma glucose concentration in females. The FS diet induced specific changes in the methylation of individual CpG in females, but not in males, which were related to the time of exposure. Methylation of CpG ? 248 increased the binding of CCAAT-enhancer-binding protein ? to the PEPCK promoter. Together, these findings show that both the period during the life course and sex influence the effect of increased exposure to folic acid on the epigenetic regulation of PEPCK and glucose homeostasis

Polyunsaturated fatty acid synthesis de novo is required for calcium release in vascular smooth muscle

<p>Previous studies show that inhibition of delta-5 desaturase and delta-6 causes a<br>decrease in phenylepherine (PE)- induced vasoconstriction in human femoral artery,<br>and in rat aorta and mesenteric arteries. These data showed that the activity of the<br>polyunsaturated fatty acid (PUFA) biosynthesis pathway related to vasoconstriction is<br>specifically located in vascular smooth muscle (VSM). The study also showed that<br>inhibiting the PUFA-biosynthesis pathway causes a decrease in the release of the proconstriction<br>eicosanoids prostaglandin (PG) F2 alpha, PGE2 and thromboxane A2 (1).<br>Activity of the PUFA biosynthesis pathway has previously been shown in arterial<br>endothelial (2) and smooth muscle cells (3). However, there is no direct evidence of the<br>exact extent of the pathway and contribution of PUFA biosynthesis to vascular function<br>in VSM is currently unknown.</p

Schematic illustrating the effect of multiple generation exposure to increased dietary fat and carbohydrate on changes in fasting plasma glucose levels with ageing.

<p>The effect of the 21% is evident form the initial generation exposed to the diet and remains unchanged following multiple generations on the diet. Exposure to the 5% diet leads to few or no effects in the initial generation exposed, however following a sustained exposure to the diet for three generations, a similar profile is reached to that of the 21% exposed group.</p