Project description:Infection during the perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) transforms brain lipid composition in the offspring and protects the neonatal brain from stroke, in part by blunting injurious immune responses. Critical to the interface between the brain and systemic circulation is the vasculature, endothelial cells in particular, that support brain homeostasis and provide a barrier to systemic infection. Here, we examined whether maternal PUFA-enriched diets exert reprograming of endothelial cell signalling in postnatal day 9 mice after modeling aspects of infection using LPS. Transcriptome analysis was performed on microvessels isolated from brains of pups from dams maintained on 3 different maternal diets from gestation day 1: standard, n-3 enriched or n-6 enriched diets. Depending on the diet, in endothelial cells LPS produced distinct regulation of pathways related to immune response, cell cycle, extracellular matrix, and angiogenesis. N-3 PUFA diet enabled higher immune reactivity in brain vasculature, while preventing imbalance of cell cycle regulation and extracellular matrix cascades that accompanied inflammatory response in standard diet. Cytokine analysis revealed a blunted LPS response in blood and brain of offspring from dams on n-3 enriched diet. Analysis of cerebral vasculature in offspring in vivo revealed no differences in vessel density. However, vessel complexity was decreased in response to LPS at 72 h in standard and n-6 diets. Thus, LPS modulates specific transcriptomic changes in brain vessels of offspring rather than major structural vessel characteristics during early life. N-3 PUFA-enriched maternal diet in part prevents an imbalance in homeostatic processes, alters inflammation and ultimately mitigates changes to the complexity of surface vessel networks that result from infection. Importantly, maternal diet may presage offspring neurovascular outcomes later in life.

Project description:Slimming is globally prevalent especially in young women, and it may contribute to the metabolic health of their offspring. Whereas some Lamarckian ideas about environmental inheritance have been dismissed, increasing evidence suggest that certain acquired traits can be transmitted to the next generation. It is therefore of great interest to determine how and to what extent a maternal lifestyle change contributes to their offspring. Here we show that enriched environment (EE) induced maternal slimming improves general health and reprograms metabolic gene expression in mice offspring. EE in mothers induced decreased body weight, adiposity, and improved glucose tolerance and insulin sensitivity. Relative to controls, their offspring exhibited improved general health such as reduced fat accumulation, enhanced metabolic parameters as well as glucose tolerance and insulin sensitivity. Maternal slimming altered the expression of 1,732 genes in the liver of offspring, with coherent downregulation of genes involved in lipid and cholesterol biosynthesis. Epigenomic profiling in offspring revealed numerous changes in cytosine methylation depending on maternal slimming, including hypermethylation of several genes involved in lipid biosynthesis, correlated with the downregulation of these genes. Maternal slimming also altered overall transcriptome patterns in mature oocytes, which contributes largely to the metabolic health and gene expression patterns in offspring. Overall, our studies suggest that maternal slimming have a beneficial role in regulating metabolic profiles in offspring, implying that it might be considered as a potential strategy to reverse the global prevalence of obesity and related metabolic syndromes. Female F0 founders were raised on a standard diet in a normal cage until 12 weeks of age, at which point they were placed into the enriched environmental cage or stayed in the normal cage (chosen at random) for 4 weeks. Males were always raised on a standard diet in the standard cage. At 16 weeks, female F0 founders were mated with males in standard conditions. After 1 or 2 days, males were removed, and pregnant females were left alone with a standard diet in the standard cage until their litters were 3 weeks of age. Note that we always used virgin males to avoid confounding effects brought about by the males. Moreover, males mated with two female groups did not differ in phenotypic data (body weight, adiposity, fasting blood glucose and insulin levels). At 3 weeks of age, partial offspring were sacrificed and the median lobe of liver was rapidly dissected out and flash-frozen in liquid N2, each from an independent mother. Samples from five control and four slimming offspring, each from different mothers, were used for DNA extraction. The samples of DNA from the control or slimming group were pooled, and the pools were used for microarray analysis.

Project description:Slimming is globally prevalent especially in young women, and it may contribute to the metabolic health of their offspring. Whereas some Lamarckian ideas about environmental inheritance have been dismissed, increasing evidence suggest that certain acquired traits can be transmitted to the next generation. It is therefore of great interest to determine how and to what extent a maternal lifestyle change contributes to their offspring. Here we show that enriched environment (EE) induced maternal slimming improves general health and reprograms metabolic gene expression in mice offspring. EE in mothers induced decreased body weight, adiposity, and improved glucose tolerance and insulin sensitivity. Relative to controls, their offspring exhibited improved general health such as reduced fat accumulation, enhanced metabolic parameters as well as glucose tolerance and insulin sensitivity. Maternal slimming altered the expression of 1,732 genes in the liver of offspring, with coherent downregulation of genes involved in lipid and cholesterol biosynthesis. Epigenomic profiling in offspring revealed numerous changes in cytosine methylation depending on maternal slimming, including hypermethylation of several genes involved in lipid biosynthesis, correlated with the downregulation of these genes. Maternal slimming also altered overall transcriptome patterns in mature oocytes, which contributes largely to the metabolic health and gene expression patterns in offspring. Overall, our studies suggest that maternal slimming have a beneficial role in regulating metabolic profiles in offspring, implying that it might be considered as a potential strategy to reverse the global prevalence of obesity and related metabolic syndromes. Female F0 founders were raised on a standard diet in a normal cage until 12 weeks of age, at which point they were placed into the enriched environmental cage or stayed in the normal cage (chosen at random) for 4 weeks. Males were always raised on a standard diet in the standard cage. At 16 weeks, female F0 founders were mated with males in standard conditions. After 1 or 2 days, males were removed, and pregnant females were left alone with a standard diet in the standard cage until their litters were 3 weeks of age. Note that we always used virgin males to avoid confounding effects brought about by the males. Moreover, males mated with two female groups did not differ in phenotypic data (body weight, adiposity, fasting blood glucose and insulin levels). At 3 weeks of age, partial offspring were sacrificed and the median lobe of liver was rapidly dissected out and flash-frozen in liquid N2, each from an independent mother. Samples from five control and four slimming offspring, each from different mothers, were chosen for microarray analysis.

Project description:Slimming is globally prevalent especially in young women, and it may contribute to the metabolic health of their offspring. Whereas some Lamarckian ideas about environmental inheritance have been dismissed, increasing evidence suggest that certain acquired traits can be transmitted to the next generation. It is therefore of great interest to determine how and to what extent a maternal lifestyle change contributes to their offspring. Here we show that enriched environment (EE) induced maternal slimming improves general health and reprograms metabolic gene expression in mice offspring. EE in mothers induced decreased body weight, adiposity, and improved glucose tolerance and insulin sensitivity. Relative to controls, their offspring exhibited improved general health such as reduced fat accumulation, enhanced metabolic parameters as well as glucose tolerance and insulin sensitivity. Maternal slimming altered the expression of 1,732 genes in the liver of offspring, with coherent downregulation of genes involved in lipid and cholesterol biosynthesis. Epigenomic profiling in offspring revealed numerous changes in cytosine methylation depending on maternal slimming, including hypermethylation of several genes involved in lipid biosynthesis, correlated with the downregulation of these genes. Maternal slimming also altered overall transcriptome patterns in mature oocytes, which contributes largely to the metabolic health and gene expression patterns in offspring. Overall, our studies suggest that maternal slimming have a beneficial role in regulating metabolic profiles in offspring, implying that it might be considered as a potential strategy to reverse the global prevalence of obesity and related metabolic syndromes. Examination of the effect of 2 different maternal lifestyles, control and slimming, on the mRNA expression in the mature oocytes of the female mice. Naturally ovulated mature oocytes (MII stage) were collected from 3 control and 3 slimming female F0 founders (3 oocytes per mouse, 9 oocytes for each group).

Dataset Information

Enriched environment-induced maternal weight loss reprograms metabolic gene expression in mouse offspring.

Publications

Enriched environment-induced maternal weight loss reprograms metabolic gene expression in mouse offspring.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets