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Genome Information for Rattus norvegicus
Thiazolidinediones increase tissue insulin sensitivity and are protective against worsening of nephropathy and hypertension in diabetes. Mechanisms underlying protection at the renal level likely involve a variety of unknown changes in gene expression. We examined kidney gene expression in obese and lean Zucker rats in response to rosiglitazone (Avandia®), a peroxisome proliferator activated receptor (gamma-subtype) agonist. Lean and obese Zucker rats were treated with either control chow or chow with added rosiglitazone (3 mg/kg•bw) for 12 weeks (n = 3/group). Total kidney mRNA expression was evaluated using the Affymetrix Rat Genome 230 2.0 GeneChip. 903 probe sets were significantly (P < 0.05) altered with at least 1.5-fold changes between groups. In untreated obese rats, 300 probe sets were increased and 244 decreased, relative to lean. Increased genes included the β-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter, and aquaporin 3. Decreased genes included angiotensin converting enzyme, type 1 (ACE1). FatiGO analysis showed that the highest number of altered genes between lean and obese belonged to the categories: ion binding, hydrolase activity, and protein binding. RGZ increased expression of uncoupling protein 1 (UCP1), CD36, and fatty acid binding protein 4 (FAbp4) in both lean and obese rats. In obese rats, 33 genes were normalized by RGZ (no longer different from lean) including ACE1, fatty acid synthase (Fasn), and stearoyl-coenzyme A desaturase 2 (Scd2). Ingenuity Pathways System analysis of genes upregulated by RGZ in obese rats revealed two major nodes affected: PPAR-gamma and tumor necrosis factor alpha (TNF-alpha).
Keywords: Thiazolidinediones, PPAR-gamma agonists, renal, type II diabetes, obesity
Overall design: Twelve male Zucker rats (6 Lean and 6 Obese) were used in the study. Three rats from each body type were fed either with control diet (ground chow diet) or control diet with rosiglitazone (3 mg/kg body weight). The rats were weighed weekly and fed diets and recieved water ad libitum for 12 weeks.
Accession | PRJNA98235; GEO: GSE7193 |
Data Type | Transcriptome or Gene expression |
Scope | Multiisolate |
Organism | Rattus norvegicus[Taxonomy ID: 10116] Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus; Rattus norvegicus |
Publications | Song J et al., "Chronic rosiglitazone therapy normalizes expression of ACE1, SCD1 and other genes in the kidney of obese Zucker rats as determined by microarray analysis.", Exp Clin Endocrinol Diabetes, 2008 Jun;116(6):315-25 |
Submission | Registration date: 4-Mar-2008 Georgetown University |
Relevance | Model Organism |
Project Data:
Resource Name | Number of Links |
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Publications |
PubMed | 1 |
Other datasets |
GEO DataSets | 2 |
GEO Data DetailsParameter | Value |
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Data volume, Spots | 373188 |
Data volume, Processed Mbytes | 12 |
Data volume, Supplementary Mbytes | 151 |