Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Liver expression data from lactating QSi5 mice

ABSTRACT: The liver plays a crucial role in energy partitioning and is particularly important for the increased demand from the mammary gland during lactation. The present study identifies genes associated with negative energy balance in lactating mice. We used microarrays to detail the gene expression underlying negative energy balance and identified distinct classes of up-regulated genes. The pregnant mice was fed a high GI diet during and throughout pregnancy until peak lactation (HGI group; n = 5). The second group was fed a low GI diet over the same period (LGI group; n = 5). The HGI diet included 51.4% (W/W basis) of glucose and a gross energy of 15.6MJ/Kg and the LGI diet contained 51.4% (W/W basis) of high amylase starch (Hi-Maze) and a gross energy of 16.3MJ/Kg. At the end of this period, mice were euthanazed and livers were removed and microarray was performed.

ORGANISM(S): Mus musculus

SUBMITTER: SJ Arun

PROVIDER: E-GEOD-25616 | 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:Nutrient deficiency during perinatal development is associated with an increased risk to develop obesity, diabetes and hypertension in adulthood. However, the molecular mechanisms underlying the developmental programming of the metabolic syndrome remain largely unknown. Given the essential role of the hypothalamus in the integration of nutritional, endocrine and neuronal cues, here we have analyzed the profile of the hypothalamus transcriptome in 180-day-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet throughout pregnancy and lactation. From a total of 26,209 examined genes, 688 were up-regulated and 309 down-regulated (P<0.003) by early protein restriction. Based on the hypothesis that variations in gene expression levels often reflect changes in gene’s activity and that transcriptional networks are at the heart of physiological functions, we identified two gene clusters regulating common cellular processes whose expression is coordinately regulated by perinatal protein restriction. The first one is constituted by several genes of the insulin signaling pathway which, additionally, act as gatekeeper genes for regulation of nutrient sensing. The second cluster encompasses a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel which, in addition, link temporal and nutritional cues to metabolism through their tight interaction with the circadian clock. Collectively, these results indicate that the programming of the hypothalamic circuits regulating energy homeostasis is a key step in the development of obesity associated with malnutrition in early life and provide a valuable starting point for the direct and systematic experimental analysis of the role of the hypothalamus in the physiopathological disturbances associated with the programming of the metabolic syndrome. Five rats fed a control diet, and five rats fed a low-protein diet. All rats are male.

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Liver expression data from lactating QSi5 mice

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