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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Obesity, rather than diet, drives epigenomic alterations in colonic epithelium resembling cancer progression

ABSTRACT: High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients. ChIP sequencing of active enhancer mark h3k27ac in colon epithelium from wild type mice and NAG-1 transgenic mice treated with either low-fat diet or high-fat diet. The gene expression component of the study is included in GSE46843.

ORGANISM(S): Mus musculus

SUBMITTER: ruifang li

PROVIDER: E-GEOD-46748 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Obesity primes the enhancer landscape of colon epithelium for cancer

Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon-specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients. We measured gene expression in colon epithelium from wild type mice and NAG-1 (non-steroidal anti-inflammatory drug (NSAID)-activated gene-1) transgenic mice fed either a 10% fat diet (LF) or a 60% fat diet (HF) for 20 weeks, using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol. The ChIP-seq component of the study is included in GSE46748.

2014-01-13 | E-GEOD-46843 | biostudies-arrayexpress

Transcription profiling of colon mucosa from rats fed a high fat, high sucrose, low fibre diet with and without red wine polyphenols

Project description:In the experiment two groups of rats were compared. The control group consisted of 10 male, 5- to 6-weeks old, Fischer 344 (F344) rats (Nossan, Correzzana, Milan, Italy) fed a high fat, high sucrose, low fibre diet (control diet) for two weeks. This diet was based on the AIN76 diet [19], and was modified to contain 23% (w/w) fat (from corn oil) and a low level of cellulose (2% w/w), to mimic the high risk of colon cancer in human populations consuming high fat diets. The experimental group consisted of 10 male, 4- to 5-weeks old, F344 rats fed the same high fat diet as the control group in combination with 50 mg/kg red wine polyphenols for two weeks. The red wine polyphenol extract was prepared as described by Femia et al.<br> Total RNA was extracted using the RNeasy Midi kit (Qiagen, Milan, Italy). Equally amounts of RNA extracted from the colon mucosa of control diet-fed rats (n=10) were pooled and used as common reference for all hybridizations.

2007-11-13 | E-MEXP-934 | biostudies-arrayexpress

Maternal exposure to a Western-style diet causes differences in microbiota composition and gene expression in the intestine of suckling mouse pups

Project description:During the last few decades, the long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident, but the effects of maternal nutrition on the developing intestine are currently still relatively underexplored. In this study, we investigated in mice the effects of a maternal Western-style (WS) high fat/cholesterol diet, given during the perinatal period, on gene expression and microbiota composition of two-week-old offspring. Microarray analysis revealed that a perinatal WS diet caused significant changes in gene expression in the small intestine and colon of the suckling offspring. A strong sexually dimorphic effect was observed in the affected genes. However, pathway analysis of the differentially expressed genes displayed that in both sexes metabolic and immune functions were strongly affected. Integration of the microbiota and gene expression data applying a multivariate correlation analyses revealed that Bacteroidaceae, Porphyromonadaceae and Lachnospiraceae were the bacterial families that most strongly correlated with gene expression in the colon and not with the bacterial families displaying the most pronounced change due to perinatal exposure to a WS diet. Amongst the genes demonstrating a strong correlation with one or more bacterial families were genes of key importance for intestinal development or functioning (i.e., Pitx2 and Ace2). In conclusion, our data demonstrate a strong programming effect of a maternal WS diet on the development of the intestine in the offspring. Small intestine and colon were isolated from two-week-old pups of dams fed a low- or Western-style high fat/cholesterol diet and subjected to gene expression profiling.

2016-08-22 | E-GEOD-72705 | biostudies-arrayexpress

Epigenetic analysis of healthy young men following a control and high-fat overfeeding diet

Project description:Genome-wide DNA methylation profiling of healthy young men following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle. Randomized cross-over desgin, where all subjects receieved both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 23 different individuals amounting to 22 samples following the control diet and 22 samples following the high-fat overfeeding diet (paired n=21). Bisulphite converted DNA from the 44 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.

2012-09-12 | E-GEOD-36166 | biostudies-arrayexpress

Fat BodFat Body, Hungry Brain: Nutriproteomics in the Hypothalamus from a Mouse Model with Obesity and Anorexiay, Hungry Brain: Nutriproteomics in the Hypothalamus from a Mouse Model with Obesity and Anorexia

Project description:Systemic acute inflammatory signals can cause profound anorexia by disrupting the physiological appetite regulation in the hypothalamic milieu. Conversely, obesity related chronic inflammation of the hypothalamus can disturb anorexigenic signals and promote abnormal body weight control. The aim of the present study was to compare the global hypothalamic endophenotype in C57/Bl6 mice exposed to a high-fat diet or with acute illness mediated by LPS. Ten-week old male C57/Bl6 mice (n=18) were randomly divided into four groups; the control 1 group (n =3) was fed a normal diet whereas the high-fat diet (HFD) group (n =6) was fed a high-fat diet for eight weeks. The control 2 group (n=3) received an intraperitoneal injection of saline whereas the LPS group (n=6) received an intraperitoneal injection of LPS. Mice were sacrificed 18-hr post-injection. Both control 2 and LPS groups were fed a normal diet for eight weeks before the injection. The hypothalamic regions were removed and analysed using a 2D LC-MS methodology. The proteomic analysis profiled 9,235 proteins (q<0.05) across all biological states, of which 522 proteins were found modulated in the HFD group and another 579 in the LPS group. The proteomic profiles demonstrated that the systemic acute inflammation linked with anorexia induced a negative feedback loop of appetite control in the hypothalamus, suggesting an effort to re-establish homeostasis. By contrast, the chronic inflammation associated with obesity initiated a “perpetual cycle” of positive feedback enhancement of appetite regulation further exacerbating positive energy balance.

2018-01-29 | PXD002119 | Pride

Are you also what Your Mother Eats? Distinct Proteomic Portrait as a Result of Maternal High-Fat Diet in the Cerebral Cortex of the Adult Mouse.

Project description:Background: Epidemiological studies suggest an association between maternal obesity and adverse neurodevelopmental outcomes in offspring. Objective: To compare the global proteomic portrait in the cerebral cortex between mice born to mothers on a high-fat or control diet who themselves were fed a high-fat or control diet. Methods: Male mice born to dams fed a control (C) or high fat (H) diet four weeks before conception and during gestation and lactation were assigned to either C or H diet at weaning. Mice (n=24) were sacrificed at 19-weeks and their cerebral cortices were pooled into 8 samples and analysed using an iTRAQ based 2D LC-MS methodology. Results: A total of 6,695 proteins were identified and fully quantified (q<0.01). Approximately 10% of these proteins demonstrated a minimum of one Standard Deviation of regulation across all biological replicates in at least one of the experimental groups (CH, HC, HH) relative to the control (CC). Principal component analysis and hierarchical clustering analysis showed that mice clustered based on the diet of the mother and not their current diet. In silico bioinformatics analysis revealed that maternal high-fat diet was significantly associated with response to hypoxia/oxidative stress and apoptosis in the cerebral cortex of the adult offspring. Conclusion: Maternal high-fat diet was associated with distinct endophenotypic changes of the adult mouse cerebral cortex independent of the diet of the offspring. The identified modulated proteins could represent novel therapeutic targets for the prevention of neuropathological features resulting from maternal obesity.

2018-01-29 | PXD001540 | Pride

Transcription profiling of livers of C57BL/6 mice and LDL receptor deficient mice fed on either low fat or high fat diet to study liver gene expression associated with diet.

Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver

2007-11-01 | E-GEOD-363 | biostudies-arrayexpress

Changes in the expression of miRs in the aorta after 3 and 10 months of a high fat diet compared with normal diet

Project description:We tried to identify miRs that are differentially expresssed during atherogenesis. Aortic miRs expression profile in female apoe-/- mice after 3 and 10 months of a high fat diet were compared with female apoe-/- mice on normal diet. 4 Female apoe-/- mice (6-8 weeks) were fed on high fat diet for 3 months. 3 female apoe-/- mice (6-8 weeks) were fed on high fat diet for 10 months. 4 female apoe-/- mice (6-8 weeks) on normal diet served as controls. Total RNA was isolated from whole aortic tissue. RNA samples with RIN>8 were used for array. The aortic miRs expression profile after 3 months of a high fat diet was compared with the control group. Biological replicates: 4 per group. One replicate per array.

2014-01-01 | E-GEOD-26557 | biostudies-arrayexpress

Epigenetic analysis of men with low birth weight following a control and high-fat overfeeding diet

Project description:Genome-wide DNA methylation profiling of young men born with low birth weight following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle. Randomized cross-over desgin, where all subjects receieved both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 17 different individuals amounting to 16 samples following the control diet and 15 samples following the high-fat overfeeding diet (paired n=14). Bisulphite converted DNA from the 31 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.

2014-01-01 | E-GEOD-40798 | biostudies-arrayexpress

Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2)

Project description:The risk for colon cancer is associated with nutrition, especially high fat and low calcium diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation. C57BL/6 mice received a Westernized high fat and low calcium diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. RNA was isolated from colon scrapings and subjected to gene expression profiling (n=7 control mice and n=9 heme-fed mice).

2011-10-01 | E-GEOD-27848 | biostudies-arrayexpress

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