Project description:In this study, we have examined the effect of combined prenatal Lactobacillus reuteri and omega-3 fatty acid supplementation on DNA methylation patterns in neonatal immune cells from children with a high propensity of developing allergies. We addressed this matter by assessing epigenome-wide DNA methylation patterns in CD4+ T helper cells obtained at birth, using the Illumina MethylationEPIC 850K array. Samples were retrieved from all four arms of the on-going PRObiotics and OMega-3 (PROOM-3, ClinicalTrials.gov-ID: NCT01542970) allergy prevention trial, and treatment-induced differential methylation as well as network modules were assessed.
Project description:Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (krill oil) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects. Twenty-one microarrays: three diets (CO, FO, KO) x seven mice per diet x one microarray per mouse
Project description:Feeding dams during gestation affects the development of the offspring for their entire life. The objective of the current experiment was to evaluate the changes of the transcriptome in the hypothalamus of the offspring lambs born from dams supplemented with: i) a control diet (without lipids or methionine supplementation), ii) an omega 3 fatty acid supplementation, or iii) a methionine supplementation. The supplementation took place in the last third of gestation and the hypothalamus of male and female offspring was collected after being on a fattening diet for 54 days. Hypothalamus samples were used to extract RNA and analyzed using RNA sequencing. There was an interaction due to sex and methionine supplementation. The pathways that were modified were chromatin structure, developmental processes, and organ morphology. The modification observed on these pathways could explain the sex-by-treatment interaction differences previously observed in growth. There was no sex by omega-3 fatty acid interaction on the hypothalamus transcriptome. Therefore, the sexual dimorphism observed by methionine supplementation may be regulated by the hypothalamus.
Project description:Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (krill oil) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects.
Project description:identification of the effect of transgenerationnal supplementation with omega 3 fatty acids on the resistance to a diet induced obesity challenge identification of the effect of transgenerationnal supplementation with omega 3 fatty acids on the resistance to a diet induced obesity challenge
Project description:The hypothesis was that 6 months of dietary n-3 FA supplementation to humans affected expression of genes that might be of significance for inflammatory processes and for Alzheimer´s disease. Effects on global gene expression profiles (Affymetrix Human Focus array) in human blood mononuclear leukocytes obtained from 11 patients with Alzheimer´s disease before and after 6 months of a DHA-rich n-3 fatty acid supplementation. Data analyses were performed using Gene chip Operating Software (GCOS) Version 1.4. Two Samples, GSM735991 and GSM736014, are missing CEL files due to storage failure.
Project description:Agricultural workers are at risk for the development of acute and chronic lung diseases due to their exposure to organic agricultural dusts. A diet intervention using the omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to be an effective therapeutic approach for alleviating a dust-induced inflammatory response. We thus hypothesized a high-DHA diet would alter the dust-induced inflammatory response through the increased production of specialized pro-resolving mediators (SPMs). Mice were pre-treated with a DHA-rich diet 4 week s before being intranasally challenged with a single dose of an extract made from dust collected from a concentrated swine feeding operation (HDE ). This omega-3-fatty-acid-rich diet led to reduced arachidonic acid levels in the blood, enhanced macrophage recruitment, and increased the production of the DHA-derived SPM Resolvin D1 (RvD1) in the lung following HDE exposure. An assessment of transcript-level changes in the immune response demonstrated significant differences in immune pathway activation and alterations of numerous macrophage-associated genes among HDE-challenged mice fed a high DHA diet. Our data indicate that consuming a DHA-rich diet leads to the enhanced production of SPMs during an acute inflammatory challenge to dust, supporting a role for dietary DHA supplementation as a potential therapeutic strategy for reducing dust-induced lung inflammation.
Project description:The objective of this project is identifying differentially expressed (DE) genes which are associated with higher omega-3 fatty acids deposition in beef cows. Omega-3 fatty acids have been found to influence meat flavor and are beneficial to human health. Supplementation of livestock diets with flaxseed, a rich source of ë±-linolenic acid, is the most common means of producing omega-3 fatty acid-enriched animal products. Towards the goal of enhancing beef fatty acid composition, 64 crossbred cull cows (~30 months of age) with similar breed composition were randomized by weight/body condition, and fed one of four 50:50 forage:concentrate diets on a DM basis (16 cows/treatment), containing ground barley grain with either hay or silage, supplemented with 0 or 15% ground flaxseed (DM basis). Cows were slaughtered after spending 140 days on the treatment diets. Five cows from each of the four diets were selected for transcriptional analysis based on FA profiles of the kidney fat collected at slaughter. RNA was isolated from Longissimus thoracis muscle, subcutaneous and kidney fat of each cow (20 samples/tissue) and hybridized in duplicate to BOMC 24K 60-mer microarrays. Differential gene expression between flax-fed and non-flax-fed cows as well as identifying those genes associated with fatty acid metabolism were studied.
Project description:Study question: Do short-term and long-term exposures to low dose folic acid supplementation alter DNA methylation in sperm? Summary answer: No alterations in sperm DNA methylation patterns were found following the administration of low dose folic acid supplements of 400 μg/day for 90 days (short-term exposure) or when pre-fortification of food with folic acid and post-fortification sperm samples (long-term exposure) were compared. What is known already: Excess dietary folate may be detrimental to health and DNA methylation profiles due to folate’s role in one carbon metabolism and the formation of S-adenosyl methionine, the universal methyl donor. DNA methylation patterns are established in developing male germ cells and have been suggested to be affected by high dose (5 mg/day) folic acid supplementation. Participants/materials, setting, methods: Blood and seminal plasma folate levels were measured in participants before and following the 90-day treatment with placebo or supplement. Sperm DNA methylation was assessed using the whole genome and genome-wide techniques, MassArray epityper, restriction landmark genomic scanning, methyl-CpG immunoprecipitation and Illumina HumanMethylation450 Bead Array. Main results and the role of chance: Following treatment, supplemented individuals had significantly higher levels of blood and seminal plasma folates compared to placebo. Initial first generation genome-wide analyses of sperm DNA methylation showed little evidence of changes when comparing pre- and post-treatment samples. With Illumina HumanMethylation450 BeadChip arrays, no significant changes were observed in individual probes following low-level supplementation; when compared with those of the post-fortification cohort, there were also few differences in methylation despite exposure to years of fortified foods. Limitations, reasons for caution: This study was limited to the number of participants available in each cohort, in particular those who were not exposed to early (pre-1998) fortification of food with folic acid. While genome-wide DNA methylation was assessed with several techniques that targeted genic and CpG rich regions, intergenic regions were less well interrogated. Wider implications of the findings: Overall, our findings provide evidence that short term exposure to low dose folic acid supplements of 400 μg/day, over a period of 3 months, a duration of time that might occur during infertility treatments, has no major impact on the sperm DNA methylome.
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.