Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Profiling adipose tissue (eWAT) from obese ob/ob and lean control ob/+ mice

ABSTRACT: This program addresses the molecular basis of beta-cell failure associated with the development of type 2 diabetes in the db/db mice. Specifically, which genes are differentially expressed in pancreatic islets of the db/db mice compared to the control db/+ mice? The db/db mice islets profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in the islets of db/db mice compared to the corresponding db/+ controls.

ORGANISM(S): Mus musculus

SUBMITTER: I-Ming Wang

PROVIDER: E-GEOD-31952 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers.

Wang I-Ming IM Zhang Bin B Yang Xia X Zhu Jun J Stepaniants Serguei S Zhang Chunsheng C Meng Qingying Q Peters Mette M He Yudong Y Ni Chester C Slipetz Deborah D Crackower Michael A MA Houshyar Hani H Tan Christopher M CM Asante-Appiah Ernest E O'Neill Gary G Luo Mingjuan Jane MJ Thieringer Rolf R Yuan Jeffrey J Chiu Chi-Sung CS Lum Pek Yee PY Lamb John J Boie Yves Y Wilkinson Hilary A HA Schadt Eric E EE Dai Hongyue H Roberts Christopher C

Molecular systems biology 20120717

Common inflammatome gene signatures as well as disease-specific signatures were identified by analyzing 12 expression profiling data sets derived from 9 different tissues isolated from 11 rodent inflammatory disease models. The inflammatome signature significantly overlaps with known drug targets and co-expressed gene modules linked to metabolic disorders and cancer. A large proportion of genes in this signature are tightly connected in tissue-specific Bayesian networks (BNs) built from multiple ...[more]

PMID: 22806142

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Project description:BACKGOUND: Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can have harmful consequences for the liver, especially in the context of obesity. OBJECTIVES: To determine whether chronic, low dose exposure to pharmaceuticals could have deleterious effects in livers of lean and obese mice. METHODS: Lean and ob/ob male mice (5-week-old) were treated for 4 months with a mixture of 11 drugs (acetaminophen, caffeine, carbamazepine, cotinine, diclofenac, erythromycin, ibuprofen, phenazone, roxithromycin, salicylic acid and sulfamethoxazole) provided in drinking water at a concentration of 1 mg/L (for each drug). At the end of the treatment, investigations were performed in liver and plasma. RESULTS: Some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 1 mg/L of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals indicated that expression of 8 different circadian genes was significantly modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 100-1,000 ng/L. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were confirmed in an independent study performed in female mice. CONCLUSIONS: Chronic, low dose exposure to pharmaceuticals disturbed hepatic expression of circadian genes, especially in obese mice. Because some of the 11 drugs can be found in the drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, in particular for obese individuals exposed to these contaminants. C57BL/6J lean and ob/ob male mice (5-week-old) were treated for 4 months with a mixture of 11 drugs provided in drinking water at a concentration of 1 mg/L (for each drug). 4 groups were designed: untreated versus treated WT and ob/ob mice (n=6 mice per group).

Dataset Information

Profiling adipose tissue (eWAT) from obese ob/ob and lean control ob/+ mice

Publications

Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers.

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