Female- and male-specific transcriptomic and epigenetic placental signatures in response to a maternal high fat diet in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jean-Philippe Jais
PROVIDER: E-GEOD-29585 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Chronic exposure to inorganic arsenic (iAs) or a high-fat diet (HFD) can produce liver injury. However, the interactive molecular biological effects and mechanism of iAs and HFD are as of yet unclear. We used microarrays to detail the interactive effects of arsenic and a high-fat diet on hepatic gene expression. The C57BL/6 Mice fed low-fat diet (LFD) or HFD were exposed to 3 mg/L iAs or deionized water for 10 weeks. Then, hepatic RNA were extraction and hybridization on Affymetrix microarrays. Differentially expressed genes in LFD+As, HFD, and HFD+As groups compared to LFD group were identified, and interactive molecular biological effects and mechanism of iAs and HFD were discussed.
2013-11-30 | E-GEOD-52702 | biostudies-arrayexpress
Project description:We have previously reported that providing a control diet to obese and diabetic mice during the periconceptional/gestation/lactation period, led to a drastic sex-specific shift from susceptibility to resistance to high fat feeding (HFD) in the female offspring. In the present study, we aimed to characterize exhaustively the metabolic phenotype of F1 and F2 sensitive (S1, S2) and resistant (R1, R2) mice and underscore in the liver, muscle and adipose tissue, the transcriptional and epigenetic mechanisms supporting the response to HFD, the trait of resistance/susceptibility and the adaptation across generations. We report the transcriptomic analyses realized based on a candidate gene approach in the liver using a custom mouse microchip. A direct comparison strategy with dye-swapping was used to compare two conditions and dye-swaps were replicated several times with at least 4 different animals/group. The comparisons of primary interest: S1 vs N1 (S1/N1); S2 vs N2 (S2/N2); R2 vs N2 (R2/N2); R2 vs S2 (R2/S2) and S2 vs S1 (S2/S1) were made according to a design such that secondary comparisons could be estimated.
2012-03-31 | E-GEOD-30085 | biostudies-arrayexpress
Project description:Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor antagonist and a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, reportedly has beneficial effects on insulin sensitivity. We studied the effects of telmisartan on the adipose tissue macrophage phenotype in high fat-fed mice. Telmisartan was administered for 5 weeks to high fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in epididymal fat tissues were examined. Insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight and adipocyte size without affecting the amount of food intake. Telmisartan treatment reduced the number of CD11c-positive cells and crown-like structures. Telmisartan reduced the mRNA expressions of M1 macrophage markers, such as TNF-alpha and IL-6, and increased the expression of M2 markers, such as IL-10 and Mgl2. The reduction of M1 macrophage markers, as well as the increased gene expression of M2 markers especially IL-10, is a possible mechanism for the improvement of insulin sensitivity by telmisartan. Six-week-old male C57BL/6J mice were purchased from CLEA Japan. The mice were fed a chow that contained 10% of its calories from fat (control) or a high-fat diet (HFD) that contained 30% of its calories from fat for 24 weeks. The high fat-fed mice were randomized to 3 groups. Either telmisartan (~3 mg/kg/day) in drinking water (HFD+Tel), candesartan (~3 mg/kg/day) in drinking water (HFD+Can), or a HFD without any drugs (HFD) was administered for the next 5 weeks. Two mice were treated per group. Epididymal adipose tissues were rapidly removed from each mouse. Gene expression in epididymal fat tissue was analyzed using a GeneChip® system with the Mouse Genome 430 2.0 Array, which was spotted with 45,101 probe sets (Affymetrix, Santa Clara, CA, USA). Sample preparation for the array hybridization was performed according to the manufacturer’s instructions. In short, 5 μg of total RNA was used to synthesize double-stranded cDNA using the GeneChip® Expression 3′-Amplification Reagents One-Cycle cDNA Synthesis Kit (Affymetrix). Biotin-labeled cRNA was then synthesized from the cDNA using GeneChip® Expression 3′-Amplification Reagents for IVT Labeling (Affymetrix). After fragmentation, the biotinylated cRNA was hybridized to arrays at 45 °C for 16 h. The arrays were washed, stained with streptavidin-phycoerythrin, and scanned using a probe array scanner. The scanned chip was analyzed using the GeneChip Analysis Suite software (Affymetrix). Hybridization intensity data were converted into a presence/absence call for each gene, and changes in gene expression between experiments were detected by a comparison analysis. Data was shown as the fold change relative to the expression level of normal chow-fed mice.
2010-01-22 | E-GEOD-19954 | biostudies-arrayexpress
Project description:Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem cells (ISCs) of the mammalian intestine. Like HFD, ex vivo treatment of intestinal organoid cultures with palmitic acid (PA), a constituent of the HFD, enhances the self-renewal potential of these organoid bodies. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-delta signature in intestinal stem and progenitor cells and pharmacologic activation of PPAR-delta recapitulates the effects that HFD has on these cells. Interestingly, HFD- and agonist-activated PPAR-delta signaling endows organoid-initiating capacity to non-stem cells and enforced PPAR-delta signaling permits these non-stem cells to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-delta activation alters not only the function of intestinal stem and progenitor cells but also their capacity to initiate tumors. mRNA profiles of intestinal stem cells (GFP-Hi) and progenitors (GFP-Low) from WT or HFD fed mice were generated by deep sequencing using HiSeq 2000.
2016-02-16 | E-GEOD-67324 | biostudies-arrayexpress
Project description:Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Liver samples were extracted and hybridized to Affymetrix Genome U74 (version 2) arrays.
2007-04-06 | E-CBIL-24 | biostudies-arrayexpress
Project description:Global deficiency of catalytic subunit Ppp3cb, and tissue-specific ablation of regulatory subunit Ppp3r1 from skeletal muscle but not adipose tissue or liver led to protection from high-fat diet induced obesity and comorbid sequelæ. Ser637 hyperphosphorylation of dynamin-related protein 1 (Drp1) in skeletal muscle of calcineurin-deficient mice was associated with mitochondrial elongation into power-cable shaped filaments, increased mitochondrial respiration, but attenuated exercise performance. Mice used for microarray analyses were all male, and chronically exposed to HFD for at least 8 weeks.
2015-07-22 | E-GEOD-71174 | biostudies-arrayexpress
Project description:Mice were fed for 2, 10 or 30 days with a normal chow (NC) or a high fat diet (HFD). At each time point, mice were sacrificed and liver samples were collected and immediately frozen in liquid nitrogen. Total RNA from each sample was further extracted, purified, quality-controled before and after amplification. Cy3-labeled RNA from individual liver sample was co-hybridized with a Cy5-labeled pool of RNA on the mouse 17K microarray. Keywords: diet response, time course, mouse strains For a given time point, each individual RNA sample was hybridized with a pool of RNA from 6 mice
2009-08-09 | E-GEOD-12409 | biostudies-arrayexpress
Project description:Gene expression in livers of male wild-type (WT) and OGG1-deficient (Ogg1-/-) mice fed either a chow diet or a high-fat diet (HFD) were examined. Mice were fed the diet for 10 weeks prior to tissue collection and were 22 weeks of age at the time of tissue collection. 24 Total samples were analyzed. We generated the following pairwise comparisons using GeneSifter: WT Chow vs Ogg1-/- Chow; WT HFD vs. Ogg1-/- HFD using t-test followed by Benjamini and Hochberg correction. An adjusted p-value less than 0.05 was considered to be statistically significant.
2012-12-16 | E-GEOD-35497 | biostudies-arrayexpress
Project description:The present study was constructed to confirm previous findings that mice on a high fat diet (HFD) treated by subcutaneous injection with exenatide (EXE) at 3µg/kg once daily for 6 weeks develop exocrine pancreatic injury (Rouse et al. 2014). The present study included 12 weeks of EXE exposure at multiple concentrations (3, 10, or 30 Œºg/kg) with multiple endpoints (histopathology evaluations, immunoassay for cytokines, immunostaining of the pancreas, serum chemistries and measurement of trypsin, amylase, and, lipase, and gene expression profiles). Time- and dose-dependent exocrine pancreatic injury was observed in mice associated with EXE exposure in a HFD environment. The time- and dose-dependent morphological changes identified in the pancreas involved acinar cell injury and death (autophagy, apoptosis, necrosis, and atrophy), cell adaptations (hypertrophy and hyperplasia), and cell survival (regeneration) accompanied with varying degrees of inflammatory response leading to secondary injury in pancreatic blood vessels, ducts, and adipose tissues. Gene expression profiles supported the presence of increased signaling for cell survival and altered lipid metabolism. The potential for EXE to cause acute or early chronic pancreatic injury was identified in a HFD environment. In human disease, the influence of pancreatitis risk factors or pre-existing chronic pancreatitis on this injury potential requires further investigation. Male C57BL/6 mice 6 to 8 weeks of age were purchased from Harlan Laboratories (Frederick, MD). Mice were housed individually in an environmentally controlled room (18C-21C, 40%-70% relative humidity) with a twelve-hour light/dark cycle. Mice were initially fed Certified Purina Rodent Chow #5002 (Ralston Purina Co., St. Louis, MO) providing 63% of calories through carbohydrates, 24% from protein, and 13% from fat. Per the experimental design, mice were subsequently placed on a Teklad Custom Research Diet, TD.06415 (Harlan, Frederick, MD), providing 45% of calories through fats (36% saturated, 47% monounsaturated, 17% polyunsaturated), 36% from carbohydrates, and 19% from protein. Water and food were available ad libitum. Thorough out the experiment all mice were weighed weekly and dosing adjusted accordingly for each mouse. A cohort of eighty 6 to 8 week-old male C57BL6 mice were received from Harlan Laboratories. The cohort represented experimental time point of 12 weeks. The cohort was further divided into 4 exenatide (EXE) treatment groups (0, 3, 10, or 30 ug/kg) of 20 mice each. Initially, all mice were placed on HFD for six weeks without additional treatment and were then maintained on HFD for an additional 12 weeks while receiving daily subcutaneous injections of saline or EXE (Creative Peptides, Shirley, NY; 3, 10, or 30 ug/kg). At the 12 week timepoint, twenty-four hours following their final dose, the mice from the treatment cohort were anesthetized with isoflurane and euthanized by exsanguination with collection of blood for serum harvest. The pancreas from 12 mice in each cohort was preserved in 10% formalin for histology processing. The pancreas from 5 mice in each cohort was placed in RNAlater (Life Technologies, Grand Island, NY) for subsequent RNA extraction and the pancreas from 3 mice in each cohort was immediately frozen in liquid nitrogen and then stored at -80C. Pancreas tissue was resected, preserved in RNALater, and stored at -80 C. After thawing, 2.5 mg of each sample were processed using miRNeasy Mini Kits (Cat # 217004) (Qiagen, Valencia, CA). Samples were homogenized in 700 uL of Qiazol Lysis Reagent (Qiagen), for 5 minutes at 50 hz in a TissueLyser LT (Qiagen), and processed using the automated purification of total RNA on a Qiacube (Qiagen), using the 'Purification of total RNA, including small RNAs, from animal tissues & cells (aqueous phase), version 2 (April 2010)' standard protocol, as described in the miRNeasy Mini Handbook (1073008 07/2012) & http://www.qiagen.com/QIAcube/Standard/ProtocolView.aspx?StandardProtocolID=847.Mean yield per 2.5 mg of pancreas tissue was approximately 35 ug, determined by NanoDrop spectrophotometer (Thermo Scientific, Wilmington, DE). Average RIN values were approximately 5.4 +/- 1.4, as assayed by a 2100 Bioanalyzer Instrument (Agilent Technologies, Santa Clara, CA), using an Agilent RNA 6000 Nano Kit (cat # 5067-1511). This RIN mean was consistent with our previous experiences in RNA extraction from murine pancreatic tissue. The isolated RNA was labeled and gene expression analysis performed by Expression Analysis, Inc. (Durham, NC). The 3 samples with the highest RIN from each treatment group were used to probe treatment effect on gene expression. Total RNA samples (100 ng) were converted into cDNA using Ovation WGA FFPE System (NuGEN, Part No. 6200). The second strand cDNA is then purified with Agencourt RNAClean beads and followed by SPIA amplification. Amplified SPIA cDNA product is purified using Agencourt RNAClean beads and quantitated using a NanoDrop ND-8000 spectrophotometer. Target preparation was performed using 4 ug of amplified cDNA and the NuGEN FL-Ovation cDNA Biotin Module V2. Fragmented and biotin-labeled target was hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 microarrays. Raw gene expression data were first analyzed using ArrayTrack bioinformatics tool with robust multichip average algorithm and quantile normalization. Differentially expressed genes were defined by p < 0.05 and fold change > 1.3 in Welch t-test comparing treatment and control groups. Expression data were then imported to Ingenuity Pathway Analysis (IPA) tool for further analyses of pathway, biofunction, and toxicity using general and pancreas-specific knowledge bases.
2014-06-01 | E-GEOD-54774 | biostudies-arrayexpress
Project description:Recent discovery reveals HFD insult can cause insulin resistance very rapidly, but the underlying mechanism is still not well understood. We performed a short term experiment in a Diet Induced Insulin resistance mouse model. Objective: Insulin resistance (IR) is one of the earliest predictors of type 2 diabetes. However, diagnosis of IR is limited. High fat fed mouse models provide key insights into IR. We hypothesized that early features of IR are associated with persistent changes in gene expression (GE) and endeavoured to (a) develop novel methods for improving signal:noise in analysis of human GE using mouse models; (b) identify a GE motif that accurately diagnoses IR in humans; and (c) identify novel biology associated with IR in humans. Methods: We integrated human muscle GE data with longitudinal mouse GE data and developed an unbiased three-level cross-species analysis platform (single-gene, gene-set and networks) to generate a gene expression motif (GEM) indicative of IR. A logistic regression classification model validated GEM in 3 independent human datasets (n =115). Results: This GEM of 93 genes substantially improved diagnosis of IR compared to routine clinical measures across multiple independent datasets. Individuals misclassified by GEM possessed other metabolic features raising the possibility that they represent a separate metabolic subclass. The GEM was enriched in pathways previously implicated in insulin action and revealed novel associations between β-catenin and Jak1 and IR. Functional analyses using small molecule inhibitors showed an important role for these proteins in insulin action. Conclusions: This study shows that systems approaches for identifying molecular signatures provides a powerful way to stratify individuals into discrete metabolic groups. Moreover, we speculate that the β-catenin pathway may represent a novel biomarker for IR in humans that warrant future investigation. Comparison of gene expression in muscle tissue during High Fat Diet (HFD) time course (day 5 and day 42). Chow diet will serve as control for HFD. 4 samples per group serve as experimental replicates.
2015-12-07 | E-GEOD-73036 | biostudies-arrayexpress