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Early gestational maternal low-protein diet diminishes hepatic response to fasting in young adult male mice

ABSTRACT: Maternal low-protein (MLP) diet can lead to hepatic steatosis, which only develops with ageing. It is still unclear whether the young offspring show any signs of past exposure to prenatal adverse conditions. We hypothesized that early nutritional insult would first affect the dynamic responsiveness to nutritional challenges rather than the static state. We analyzed the transcriptome and metabolome profiles of the hepatic response to fasting/refeeding in young male mice offspring to identify changes induced by early gestational MLP diet. Restricted MLP exposure strictly to early gestation was achieved by the embryo transfer method. As a result, significant transcriptional differences between control and MLP pups were found only in the fasted state. The fasting-induced upregulation of genes for long-chain fatty acid metabolism and of stress response genes related to protein folding were significantly diminished in MLP pups. Gene Set Enrichment Analysis showed that peroxisome proliferator activated receptor  (PPAR)-mediated induction was impaired in fasted MLP pups. Lipid profiling showed that the hepatic signature of triacylglycerols was shifted to longer acyl-chains and higher saturation by the MLP diet. Taken together, early gestational MLP diet affected the hepatic dynamic response to nutritional stress in seemingly healthy young offspring, accompanied with partial deterioration of PPAR action.

ORGANISM(S): Mus musculus

PROVIDER: GSE100313 | GEO | 2017/09/14

SECONDARY ACCESSION(S): PRJNA391303

REPOSITORIES: GEO

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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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Early gestational maternal low-protein diet diminishes hepatic response to fasting in young adult male mice

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