Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse liver response to a glucose challenge in healthy and insulin resistant C57BL/6J mice

ABSTRACT: The goal of this experiment is to compare the transcriptional response to a metabolic stressor (glucose bolus) between healthy and insulin resistant mouse liver. Mice with an isogenic background (C57BL/6J mice) were fed diets for 12 weeks containing either 10 or 45% fat by energy (mainly palm oil) after 2 weeks of adaptation to laboratory conditions with a control diet. The animals were subjected to a glucose tolerance test at the end of the feeding trial and liver samples were taken 0 min, 40 min, 2, 18 and 48 h after the glucose challenge. Glucose was injected via the i.p. route at 1 p.m. in all groups and animals had free access to feed during the challenge (no fasting). For more details, see Baccini et al (pmid=19034556)

ORGANISM(S): Mus musculus

SUBMITTER: Thomas Kelder

PROVIDER: E-MTAB-601 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

The NuGO proof of principle study package: a collaborative research effort of the European Nutrigenomics Organisation.

Baccini Michela M Bachmaier Eva-Maria EM Biggeri Annibale A Boekschoten Mark V MV Bouwman Freek G FG Brennan Lorraine L Caesar Robert R Cinti Saverio S Coort Susan L SL Crosley Katie K Daniel Hannelore H Drevon Christian A CA Duthie Susan S Eijssen Lars L Elliott Ruan M RM van Erk Marjan M Evelo Chris C Gibney Mike M Heim Carolin C Horgan Graham W GW Johnson Ian T IT Kelder Thomas T Kleemann Robert R Kooistra Teake T van Iersel Martijn P MP Mariman Edwin C EC Mayer Claus C McLoughlin Gerard G Müller Michael M Mulholland Francis F van Ommen Ben B Polley Abigael C AC Pujos-Guillot Estelle E Rubio-Aliaga Isabel I Roche Helen M HM de Roos Baukje B Sailer Manuela M Tonini Giulia G Williams Lynda M LM de Wit Nicole N

Genes & nutrition 20081126 3-4

PMID: 19034556

Publication: 1/2

Similar Datasets

Project description:Histone acetylation and other modifications of the chromatin are important regulators of gene expression and, consequently, may contribute to drug-induced behaviors and neuroplasticity. Previous studies have shown that a reduction on histone deacetylase (HDAC) activity results on the enhancement of some psychostimulant-induced behaviors. In the present study, we extend those seminal findings by showing that the administration of the HDAC inhibitor sodium butyrate enhances morphine-induced locomotor sensitization and conditioned place preference. In contrast, this compound has no effects on the development of morphine tolerance and dependence. Similar effects were observed for cocaine and ethanol-induced behaviors. These behavioral changes were accompanied by a selective boosting of a component of the transcriptional program activated by chronic morphine administration that included circadian clock genes and other genes relevant in addictive behavior. Our results support an specific role for histone acetylation and the epigenetic modulation of transcription at a reduced number of biologically relevant loci on non-homeostatic, long lasting, drug-induced behavioral plasticity. To further investigate the molecular bases of sodium butyrate action on long-lasting behavioral responses to morphine, we screened for potential substrates of their interaction by performing a genome-wide comparison of the striatal transcriptome after chronic administration of morphine in the absence or presence of sodium butyrate. Striatal tissue was dissected from two months-old Swiss-Albino male mice subjected to behavioral sensitization. Behavioural sensitization: Locomotor sensitization induced by morphine was evaluated using a protocol divided into two phases: induction and challenge. The induction phase involved six trials on alternate days, one trial per day. On each one of these trials, mice received and injection of saline or sodium butyrate (300 mg/kg) immediatedly followed by a second injection of morphine (20 mg/kg). The challenge phases consisted of a single trial conducted 7 days after the last test of the induction phase. In this case, all animals received a single injection of morphine (20 mg/kg). Striatal RNA was extracted 1h after the morphine challenge in groups of four animals that received either saline (N=6) or morphine (N=3), or the sodium butyrate-morphine (N=3) co-treatment during the sensitization induction phase.

Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.

Project description:Obesity and insulin resistance are two major risk factors underlying the metabolic syndrome. To gain more insight in the role of the small intestine in the etiology of these metabolic disorders, a microarray study was performed on small intestines (SI) of C57BL/6J mice that were fed a high fat diet mimicking the fatty acid composition of a Western-style human diet. The mice became obese and developed dietary fat-induced glucose intolerance. For gene expression profiling, the small intestines were subdivided in three equal parts along the longitudinal axis. The most pronounced effects of dietary fat were detected in part 2 of the small intestine. The biological processes that were most extensively modulated on a high fat diet were related to lipid metabolism, especially Î²- and Ï-fatty acid oxidation seemed to play an important role, cell cycle and inflammation/immune response. An additional secretome analysis revealed differentially expressed secreted proteins, such as Il18, Ffgf15, Mif, Igfbp3 and Angptl4, which might provoke systemic effects in peripheral organs by influencing their metabolic homeostasis. Furthermore, many of the dietary fat-modulated genes and biological processes in small intestine were previously already associated with obesity and/or insulin resistance. Together, the data of this exploratory study provided various leads for an essential role of the small intestine in development of obesity and/or insulin resistance. Experiment Overall Design: After a run-in period of 3 weeks on a low-fat diet, 9 weeks old mice were fed a high- (HF) or a low-fat (LF) purified diet for 2, 4, and 8 weeks (n=6 per diet, per time point). Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. At the end of the experiment, mice were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%). The small intestines were excised and the adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3).

Dataset Information

Transcription profiling of mouse liver response to a glucose challenge in healthy and insulin resistant C57BL/6J mice

Publications

The NuGO proof of principle study package: a collaborative research effort of the European Nutrigenomics Organisation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure