Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Maternal western diet primes susceptibility to hepatic inflamation in adult male mouse offspring

ABSTRACT: Background & Aims: The influences of the maternal diet during gestation has been suggested to be involved in the development of different aspects of the metabolic syndrome. In our mouse model we characterised the role of maternal western diet in the development of non-alcoholic fatty liver disease (NAFLD) in the offspring. Methods: Female mice were fed either a western (W) or low-fat control (L) semi-synthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. Results: Male offspring exposed to prenatal western style diet and to a post-weaning W diet (WW) showed hepatomegaly combined with increased hepatic cholesterol and triglycerides accumulation, compared to LW offspring. This was associated with up-regulation of de novo lipid synthesis and dysregulation of beta oxidation and lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. Histological analysis supported the presence of steatohepatitis in the WW offspring. In addition alterations in DNA methylation in key metabolic genes (Ppara, Insig, Fasn) were detected. Conclusion: Maternal dietary fat intake during critical developmental phases programs susceptibility to liver disease in mouse offspring. This was mediated by shifts in lipid metabolism and inflammatory response. Long lasting epigenetic changes may underlie this dysregulation 4 groups of 6 male mouse were analysed , 1 experimental and 1 biological outlier was excluded , so n=6,5,5,6 in the 4 groups (LL,LW,WL,WW)

ORGANISM(S): Mus musculus

SUBMITTER: vincent bloks

PROVIDER: E-GEOD-44901 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (pM-bM-^IM-$0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) as six weeks pre-treatment before mating, as well as during gestation and lactation. Offspring were sacrificed at postnatal week two, livers were removed and RNA samples were subjected to gene expression profiling.

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.

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Maternal western diet primes susceptibility to hepatic inflamation in adult male mouse offspring

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