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.

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

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