Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

Background: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts.

Diet and deprivation in pregnancy: a rat model to investigate the effects of the maternal diet on the growth of the dam and its offspring.

The offspring of women in the poorest socio-economic groups in Western societies have an increased risk of developing non-communicable disease in adult life. Deprivation is closely related to the consumption of a diet with an excess of energy (sugar and fat), salt and a shortage of key vitamins. To test the hypothesis that this diet adversely affects the development and long-term health of the offspring, we have formulated two rodent diets, one with a nutrient profile corresponding to the diet of pregnant women in the poorest socio-economic group (DEP) and a second that incorporated current UK recommendations for the diet in pregnancy (REC).

Iron deficiency during pregnancy and lactation modifies the fatty acid composition of the brain of neonatal rats.

Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet.

The effect of iron deficiency on the temporal changes in the expression of genes associated with fat metabolism in the pregnant rat.

Iron is essential for the oxidative metabolism of lipids. Lipid metabolism changes during gestation to meet the requirements of the growing fetus and to prepare for lactation. The temporal effects of iron deficiency during gestation were studied in female rats fed complete or iron-deficient diets.

Lipocalin-2 (Lcn2) expression is mediated by maternal nutrition during the development of the fetal liver.

The mechanisms by which maternal protein deficiency programs insulin action in the offspring are poorly understood. The interpretation of transcriptomics is complicated by homeostatic adaptations, for example, changes in amino acid metabolism, which are potentially unrelated to the programming mechanism. The fatty acid composition of the maternal diet modulates the programming of insulin action, offering a possible strategy to circumvent these complications.

A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic proteome in the adult offspring.

A methyl-deficient diet (MD) lacking folic acid and the associated methyl donors choline and methionine, fed to the laboratory rat during the periods of oocyte and embryo development, has been shown to programme glucose metabolism in the offspring. The hepatic proteome of the male offspring of female rats fed MD diets for 3 weeks prior to mating and for the first 5 days of gestation has been examined by 2-dimensional gel electrophoresis. Three groups of differentially abundant proteins associated with energy metabolism, amino acid metabolism and antioxidant defence were identified in the soluble proteins extracted from the liver from the MD offspring at both 6 and 12 months of age.

A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring.

Methyl deficiencies have been implicated in metabolic programming during the periods of oocyte and embryo development. Semisynthetic methyl-deficient diets (MD) with no folic acid, 0.05% choline, and approximately one-half the recommended content of methionine were fed to female rats for 3 wk prior to mating and for the first 5 d of gestation.

Maternal diets deficient in folic acid and related methyl donors modify mechanisms associated with lipid metabolism in the fetal liver of the rat.

Previously we have examined the effects of diets deficient in folic acid ( - F) or folate deficient with low methionine and choline ( - F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the - F diet.

Gene and protein expression profiles in the foetal liver of the pregnant rat fed a low protein diet.

Foetal growth is particularly sensitive to the protein content of the mother's diet. Microarray data from the foetal liver of pregnant rats fed normal (HP) or reduced protein diets (LP) were compared by gene set enrichment analysis. Soluble proteins from a second portion of the liver were analysed by two-dimensional gel electrophoresis.

The effects of feeding rats diets deficient in folic acid and related methyl donors on the blood pressure and glucose tolerance of the offspring.

In humans poor maternal folate status is associated with a decrease in infant birth weight. As low birth weight increases the risk of cardiovascular and metabolic disease in adults, an inadequate supply of folic acid in the mother's diet may increase the susceptibility of the offspring to disease. We have fed laboratory rats diets deficient in folic acid and the related methyl donors methionine and choline to examine the effects on growth, blood pressure and insulin action in the offspring.

Disruption of lipid metabolism in the liver of the pregnant rat fed folate-deficient and methyl donor-deficient diets.

The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (-F) or in three key methyl donors, folic acid, choline and methionine (-FLMLC) and the maternal liver was analysed on day 21 of gestation.

Folate deficiency during pregnancy impacts on methyl metabolism without affecting global DNA methylation in the rat fetus.

The methionine cycle and methyl group metabolism are implicated in the long-term programming of metabolism. Diets deficient in folic acid, methionine and choline have been fed to pregnant rats to examine the effects on amino acid metabolism, choline reserves and DNA methylation in dam and fetuses. Animals were fed folate-deficient, folate-deficient with low methionine, folate-deficient with low choline and folate-deficient, low-methionine, low-choline diets starting 2 weeks before mating.

Interactions between protein and vegetable oils in the maternal diet determine the programming of the insulin axis in the rat.

The available evidence suggests that metabolic control mechanisms are programmed early in life. Previous studies of pregnant rats fed low-protein diets have suggested that the vegetable oils used in the experimental diets influence the outcome. The present study investigated the offspring of female rats fed semi-synthetic diets containing either 180 or 90g casein/kg with 70 g/kg (w/w) of either corn oil or soya oil during gestation.

The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat.

To characterise the effects of dietary protein content on threonine metabolism during pregnancy, rats were fed diets containing 18% or 9% protein and then killed at different stages of gestation. Serum threonine concentrations fell significantly faster in the animals fed the diet containing 9% protein when compared to those fed the diet containing 18% protein. On day 4 of gestation the rate of threonine oxidation was higher in maternal liver homogenates prepared from the animals fed the diet containing 18% protein.

An imbalance in the methionine content of the maternal diet reduces postnatal growth in the rat.

The pregnant rat fed a low-protein diet has become widely used as a model system in the study of the prenatal programming of adult metabolism and disease. When pregnant rats of the hooded Lister strain were fed semisynthetic diets containing 18% or 9% casein supplemented with 0.5% dl-methionine, there was significant postnatal mortality in the group fed the low-protein diet.

Maternal protein intake in the pregnant rat programs the insulin axis and body composition in the offspring.

Evidence to support an association between early nutrition and the development of obesity in the rat is equivocal. In this study we have investigated the postnatal growth, glucose tolerance, and adipocyte function of the offspring from pregnant rats fed with diets containing either 20% or 8% protein during gestation. By 25 weeks of age, the female offspring of dams fed with the diet containing 8% protein had a significantly lower adult body weight due in part to a decrease in body fat.

The expression of growth-arrest genes in the liver and kidney of the protein-restricted rat fetus.

During fetal life, there are periods of rapid cell proliferation, which are uniquely sensitive to nutritional perturbation. Feeding the pregnant rat a protein-restricted diet alters the growth trajectory of major fetal organs such as the kidney. By day 21 of gestation, the ratio of kidney weight to total body weight is reduced in the fetuses of dams fed a protein-deficient diet.

Prenatal protein restriction does not affect the proliferation and differentiation of rat preadipocytes.

Poor development in utero may favor the development of obesity in adulthood. Animal studies showed that embryo manipulation in vitro or nutritional insults during the embryonic and fetal stages of development may lead to obesity in adult life. We studied the in vitro proliferation and differentiation of adipocytes to investigate whether early protein restriction may program cell growth and development.

Amino acid deficiency up-regulates specific mRNAs in murine embryonic cells.

The flow of amino acids to both protein and DNA synthesis is particularly important during periods of rapid cell proliferation such as the fetal stages of life. The changes in mRNA levels caused by the different types of growth arrest were studied in F9 embryonal carcinoma cells. The cells were grown in medium deficient in the amino acid lysine or in one containing phosphonoacetyl L-aspartic acid (PALA), which inhibits the incorporation of aspartic acid into pyrimidine nucleotides.