Maternal Diet Enriched with Alpha Linolenic or Saturated Fatty Acids Differentially Regulates Gene Expression in Mice Offspring's liver.
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ABSTRACT: Lipid metabolic disarray in young and adult mice offspring's liver is induced by saturated fatty acids (SFA) but prevented by alpha linolenic acid (ALA, 18:3 ω3) in the maternal diet during pregnancy and lactation. The aim of the present study was to analyse the impact of maternal dietary ALA on the liver gene expression in the new-born offspring in comparison to a SFA diet. Methods: C57Bl6/J dams were fed with diets normal in calories but rich in ALA or SFA before mating and during pregnancy. Pups were sacrificed at birth and liver parameters were assessed. Gene expression was characterized by microarray analysis and validated by real time qPCR. Results: ALA compared to SFA in maternal diets during pregnancy, increased polyunsaturated fatty acids while differentially modified fatty acid desaturase activities in offspring liver. Overall, 474 and 662 genes from born pups’ liver, were differentially regulated by ALA and SFA compared to control diet (p<0.05; Fold change 2), respectively. Notably, Per3 was up-regulated by ALA whereas down-regulated by SFA, compared to control diet. Conclusions: ALA and SFA enriched diets differentially affect gene expression pattern in the offspring’s liver. ALA in particular, upregulates genes associated to low adiposity.
Project description:Aims: Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we aim to explore phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic alterations in adulthood induced by maternal diet. Methods: We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart [GSE40903] . We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results: Maternal diet had a significant effect on the body weight of the offspring when they are fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. Maternal diet had no detectable effect on DNA methylation in the liver. Conclusions: Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver. Methylation is compared between nine week old animals fed a common diet as adults, but derived from mothers fed different diets.
Project description:Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is unknown. We investigated the effect of dietary lipid composition on human microbiota in an observational study and combined diet experiments with microbiota transplants to study lipid-microbiota interactions and liver status in mice. In humans, low intake of saturated fatty acids (SFA) was associated with increased microbial diversity independent of fiber intake. In mice, cecum levels of SFA correlated negatively with microbial diversity and were associated with a shift in butyrate and propionate producers. Mice fed poorly absorbed SFA had improved metabolism and liver status. These features were transmitted by microbial transfer. Diets enriched in n-6- and/or n-3-polyunsaturated fatty acids were protective against steatosis but had minor influence on the microbiota. In summary, we find that unabsorbed SFA correlate with microbiota features that may be targeted to decrease liver steatosis.
Project description:Aims: Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we aim to explore phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic alterations in adulthood induced by maternal diet. Methods: We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart [GSE40903] . We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results: Maternal diet had a significant effect on the body weight of the offspring when they are fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. Maternal diet had no detectable effect on DNA methylation in the liver. Conclusions: Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver. Methylation is compared between nine week old animals fed a common diet as adults, but derived from mothers fed different diets. Sequence of PCR amplification of bisulfite converted genomic DNA of numerous loci
Project description:In a randomized controlled dietary intervention study, we compared a diet enriched in polyunsaturated fatty acids (PUFA) with a diet enriched in saturated fatty acids (SFA) for influence on abdominal subcutaneous adipose tissue gene expression. We studied young lean adults; 11 women and 25 men. There was no significant difference in age, BMI, or gene expression between the PUFA and SFA groups before the intervention. The intervention lasted for seven weeks. We calculated for each gene the absolute difference in gene expression after vs. before intervention (deltas), and compared the deltas between the PUFA and SFA group using SAM. 12 genes were significantly differentially regulated by the two diets with a FDR of 25%. These include metabolic and adipokine genes. In conclusion, dietary fatty acids have a modest influence on white adipose tissue gene expression.
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.
Project description:Gestational protein restriction is a model for low birth size. We hypothesized that taurine supplementation would protect against changes in newborn liver and muscle caused by a maternal low protein diet. Pregnant mouse dams were subjected to different diet schemes from day 1 of pregnancy until birth. Pups were killed following birth and liver and hindleg skeletal muscle taken out and frozen at -80C until analysis. Diet schemes: Normal Protein (20% casein; NP), Normal Protein + taurine (1% taurine supplementation in water ad libitum; NP+tau), Low Protein (8% casein; LP) and LP+tau The liver and muscle samples were normalized separately.
Project description:Early nutritional environment affects development and long-term health. Our objective was to determine the effect of maternal high fat diet (HFD) during pregnancy and lactation on neonate`s duodenum histomorphology and proteome. Female mice were fed either a control diet (10% kcal fat; C) or a HFD (60% kcal fat) for four weeks, and bred. On postnatal day 2, litters were standardized to ten pups and half the pups were cross-fostered to dams fed on different diets, creating four treatment combinations: C-C (control), C-HF, HF-C, HF-HF. On postnatal day 12, pups` duodenum were excised and prepared for histology and LC-MS/MS analysis of proteome. Villi were significantly longer in duodenum of HF-HF pups compared to all other treatments. However, crypt cell proliferation rate was not different among treatments. Over 3000 proteins were detected, with 1054 commonly expressed across all groups. Between control and HF-HF, HF-C or C-HF, 812, 601 or 894 proteins were differentially expressed (Tukey adj-P <0.05), respectively. Functional analysis clustered proteins upregulated in HF-HF versus control in fat digestion and absorption, extracellular matrix, cell adhesion, immune response, oxidation-reduction processes, phagocytosis and transport categories. Proteins downregulated were classified as RNA splicing, translation, protein folding, endocytosis and transport. Thus the effect of nutritional environment on intestinal tract structure and function is manifested as early as postnatal day 12. In particular, exposure to maternal HFD during pregnancy and lactation changed fat digestion and absorption processes, increased extracellular matrix and focal adhesion proteins, and heightened innate and active immune response.
Project description:Obesity during pregnancy is associated with increased risk of non-alcoholic fatty liver disease in the offspring. We used RNA next generation sequencing analysis (HiSeq2000) to have a snapshot of the liver transcriptome in twelve week-old male offspring exposed to maternal obesity and weaned onto an obesogenic diet.
Project description:In a randomized controlled dietary intervention study, we compared a diet enriched in polyunsaturated fatty acids (PUFA) with a diet enriched in saturated fatty acids (SFA) for influence on abdominal subcutaneous adipose tissue gene expression. We studied young lean adults; 11 women and 25 men. There was no significant difference in age, BMI, or gene expression between the PUFA and SFA groups before the intervention. The intervention lasted for seven weeks. We calculated for each gene the absolute difference in gene expression after vs. before intervention (deltas), and compared the deltas between the PUFA and SFA group using SAM. 12 genes were significantly differentially regulated by the two diets with a FDR of 25%. These include metabolic and adipokine genes. In conclusion, dietary fatty acids have a modest influence on white adipose tissue gene expression. Abdominal subcutaneous adipose needle biopsies were obtained from young adults before (W0) and after completion (W7) of the dietary intervention. From the biopsies we extracted RNA. From total RNA we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.1 ST Arrays (Affymetrix, Inc., Santa Clara, CA), and then washed, stained and scanned the slides using standardised protocols (Affymetrix, Inc.). Signicance analysis of microarrays (SAM) was use to compare the difference in gene expression between groups.
Project description:Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy men ingested saturated (SFA) or poly unsaturated (PUFA) fat-rich diets for six weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with PUFA. In mice, eucaloric feeding of human PUFA and SFA diets lowered hepatic triacylglycerol content compared to low-fat fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.