Chronic rosiglitazone therapy normalizes expression of ACE1, SCD1 and other genes in the kidney of obese Zucker rats as determined by microarray analysis
| Autor: | Habtom W. Ressom, Liu H, Ecelbarger Cm, Tiwari S, Song J |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism CD36 Peroxisome proliferator-activated receptor Peptidyl-Dipeptidase A Kidney Gene Expression Regulation Enzymologic Nephropathy Rosiglitazone Endocrinology Ion binding Internal medicine Internal Medicine medicine Animals Obesity Oligonucleotide Array Sequence Analysis chemistry.chemical_classification Genome biology business.industry Chromosome Mapping Angiotensin-converting enzyme General Medicine medicine.disease Rats Rats Zucker Fatty acid synthase medicine.anatomical_structure chemistry biology.protein Thiazolidinediones business Stearoyl-CoA Desaturase medicine.drug |
| Zdroj: | Experimental and clinical endocrinologydiabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 116(6) |
| ISSN: | 0947-7349 |
| Popis: | 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 x 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 beta-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 (SCD1). 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). |
| Databáze: | OpenAIRE |
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