Project description:Current commercially available feeds for salmon are predominantly made of plant ingredients, with consequent changes to the composition and contents of a range of nutrients and other components in the diet. There are concerns that, with these major changes in raw materials, new feeds will affect not only the composition and contents of nutrients, but also the bioavailability and, combined with the limited knowledge of micronutrient requirements for Atlantic salmon, this might impact growth performance and health of the fish. The present study investigated the effects of graded levels of a micronutrient package supplemented to feeds formulated with low levels of marine ingredients and fed to diploid and triploid Atlantic salmon throughout the freshwater phase. Specifically, fish were fed three diets containing low levels of FM and FO and identical in formulation other than being supplemented with 3 levels (L1, 100 %; L2, 200 % and L3, 400 %) of a micronutrient mix formulated as a modification of current nutrient levels reported for salmon. Duplicate groups of diploid and triploid parr were fed the experimental diets from around 30 g to seawater transfer and the effects on growth performance, feed efficiency, biochemical composition, liver histology, hepatic gene expression (transcriptome) and smoltification efficiency determined. Microarray analysis revealed that the hepatic transcriptome profile of diploid fish fed diet L2 was more similar to that observed in triploids fed diet L3 than to those fed L2, suggesting that micronutrient requirements of triploid salmon may differ from levels accepted in diploid salmon. Different levels of micronutrient supplementation affected the expression of key genes involved in lipid metabolism. In particular sterol biosynthesis pathways (steroid and terpenoid backbone synthesis) were down-regulated in both L2-fed diploids and L3-fed triploids when compared with diet L1-fed diploids and triploids, respectively. Gene sets analysis showed an up-regulation of genes involved in immune processes in triploid salmon fed diet L3. Another biological category affected by diet in triploid salmon was genetic information processing. In fish fed diet L3 down-regulation of RNA degradation, proteasome, RNA polymerase, spliceosome and ribosome was observed, suggesting a decrease in protein turnover in this group, which may indicate a decrease in energy expenditure. In addition, one-carbon metabolism was affected by diet in diploid and triploid salmon.
Project description:The effect of pre and periconceptional multiple micronutrient supplementation on methylation of CpG loci within CpG islands associated with 14,000 genes across the human genome has been investigated in the offspring of a cohort of Gambian women participating in a controlled double blinded trial. Methylation levels in placebo and micronutrient supplemented cohorts were compared in genomic DNA from cord blood (35 placebo and 21 micronutrient supplemented) and in circulating blood samples (14 placebo and 9 micronutrient supplemented) drawn from the same cohort at 9 months old. A small number of differentially methylated CpG loci were identified in cord blood (14 in males and 21 in females) and a larger number in the 9 month infant comparison (108 in males and 106 in females). Seven differentially methylated loci in males and 8 in females persisted from cord to infant. These findings indicate that micronutrient supplementation pre-conception or early in embryonic development is potentially associated with programming of gene activity at birth, which is maintained into early infanthood. Strikingly, the loci affected by micronutrient supplementation differed between males and females, with no shared changes in cord blood and only 5 shared changes at 9 months. Additionally, a large number of CpG loci showed variation in methylation level when comparing 9-month samples to cord blood samples. These postnatal changes were more consistent between sexes, with 85% of female alterations being found as a subset of male changes in the placebo cohort and 62% of the female changes shared with males in the supplemented cohort. Taken together, the results suggest that there is a core developmental program shared between the sexes that is unaffected by nutrient supplementation, but that there are also sex-specific developmental changes which are altered under conditions of micronutrient supplementation and deficiency.
Project description:The effect of pre and periconceptional multiple micronutrient supplementation on methylation of CpG loci within CpG islands associated with 14,000 genes across the human genome has been investigated in the offspring of a cohort of Gambian women participating in a controlled double blinded trial. Methylation levels in placebo and micronutrient supplemented cohorts were compared in genomic DNA from cord blood (35 placebo and 21 micronutrient supplemented) and in circulating blood samples (14 placebo and 9 micronutrient supplemented) drawn from the same cohort at 9 months old. A small number of differentially methylated CpG loci were identified in cord blood (14 in males and 21 in females) and a larger number in the 9 month infant comparison (108 in males and 106 in females). Seven differentially methylated loci in males and 8 in females persisted from cord to infant. These findings indicate that micronutrient supplementation pre-conception or early in embryonic development is potentially associated with programming of gene activity at birth, which is maintained into early infanthood. Strikingly, the loci affected by micronutrient supplementation differed between males and females, with no shared changes in cord blood and only 5 shared changes at 9 months. Additionally, a large number of CpG loci showed variation in methylation level when comparing 9-month samples to cord blood samples. These postnatal changes were more consistent between sexes, with 85% of female alterations being found as a subset of male changes in the placebo cohort and 62% of the female changes shared with males in the supplemented cohort. Taken together, the results suggest that there is a core developmental program shared between the sexes that is unaffected by nutrient supplementation, but that there are also sex-specific developmental changes which are altered under conditions of micronutrient supplementation and deficiency. Bisulphite converted DNA from 59 cord (36 placebo and 23 treated) and 25 infant peripheral blood (15 placebo and 10 treated) samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. (For further analysis, five were excluded during quality control leaving 56 cord (35 placebo and 21 treated) and 23 infant peripheral blood (14 placebo and 9 treated) samples. Full data set of 84 samples were submitted to GEO)
Project description:Calorie restriction is a major intervention consistently demonstrated to retard aging and delay age-associated diseases. A novel micronutrient blend, a putative calorie restriction mimetic, was developed based on a screening tool we previously described. Whole transcriptomic analysis was examined in brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and unique from those in the control group. Subgroup analysis revealed that nuclear hormone receptor, proteasome complex and angiotensinogen genes, all of which are known to be directly related to the aging process, were the most affected by the micronutrient blend and by calorie restriction. Thus, these three genes may be considered master regulators of the favorable effects of calorie restriction and of the micronutrient blend. Based on the calorie restriction mimetic effects on transcriptomics, it was hypothesized that the micronutrient blend would promotes longevity and vitality. To test this hypothesis, a functional analysis in C. Elegans was used to examine the effects of the micronutrient blend on longevity and biomarkers of vitality. Results indicate that feeding C. Elegans the micronutrient blend increased longevity as well as vitality. Further studies are required to confirm that the calorie restriction mimicking benefits described here are elicited by the micronutrient blend in humans.