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Exp Clin Endocrinol Diabetes 2008; 116(6): 315-325
DOI: 10.1055/s-2008-1042429
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Chronic Rosiglitazone Therapy Normalizes Expression of ACE1, SCD1 and other Genes in the Kidney of Obese Zucker Rats as Determined by Microarray Analysis

J. Song 1 , H. Liu 2 , H. W. Ressom 3 , S. Tiwari 1 , C. M. Ecelbarger 1
  • 1Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University, Washington, DC
  • 2Center for Bioinformatics/Science Applications International Corporation, National Cancer Institute, NIH, Rockville, MD
  • 3Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
Further Information

Publication History

received 03.10.2007 first decision 04.12.2007

accepted 16.01.2008

Publication Date:
17 March 2008 (online)

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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 (γ-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 (SCD1). Ingenuity Pathways System analysis of genes upregulated by RGZ in obese rats revealed two major nodes affected: PPAR-γ and tumor necrosis factor α (TNF-α).

Key words

thiazolidinediones - PPAR-γ agonists - renal - type II diabetes - obesity

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