Abstract |
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).
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Authors | J Song, H Liu, H W Ressom, S Tiwari, C M Ecelbarger |
Journal | Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
(Exp Clin Endocrinol Diabetes)
Vol. 116
Issue 6
Pg. 315-25
(Jun 2008)
ISSN: 0947-7349 [Print] Germany |
PMID | 18700276
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Thiazolidinediones
- Rosiglitazone
- Stearoyl-CoA Desaturase
- Peptidyl-Dipeptidase A
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Topics |
- Animals
- Chromosome Mapping
- Gene Expression Regulation, Enzymologic
- Genome
- Kidney
(enzymology)
- Male
- Obesity
(drug therapy, enzymology, genetics)
- Oligonucleotide Array Sequence Analysis
- Peptidyl-Dipeptidase A
(genetics)
- Rats
- Rats, Zucker
- Rosiglitazone
- Stearoyl-CoA Desaturase
(genetics)
- Thiazolidinediones
(therapeutic use)
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