Dataset Information

Rosiglitazone effects on kidney gene expression

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•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

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE7193 | GEO | 2008/03/04

SECONDARY ACCESSION(S): PRJNA98235

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description: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 (AvandiaÂ®), 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/kgâ?¢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 Î²-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). Experiment 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.

Project description:Ecdysteroids are a class of steroid hormones occurring in insects, where they are referred as zooecdysteroids, and in plants, where they are termed phytoecdysteroids. While zooecdysteroids in insects regulate important developmental processes, such as embryogenesis, molting (ecdysis), metamorphosis, reproduction, and diapause, phytoecdysteroids provide protection against invertebrate predators by acting as feeding deterrents and by disrupting critical developmental processes of such invertebrates. The ecdysteroids in insects and plants comprise a great number of different analogues, with 20‐hydroxyecdysone, also called ecdysterone, being the quantitatively dominating biologically active analogue in both, insects and plants. Although phytoecdysteroids are effective toxins or antifeedants towards non-adapted herbivorous invertebrate predators, ecdysteroids are apparently non-toxic to mammals and even have been shown to exert a variety of interesting metabolic actions, such as antiobesity, hypoglycemic and protein-anabolic effects. In the present study aimed to test the hypothesis that ecdysterone causes lipid-lowering effects in obese Zucker rats. To test this hypothesis, two groups of obese Zucker rats were fed a nutrient-adequate diet supplemented without or with 0.05% ecdysterone. This ecdysterone concentration was appropriate to achieve a similar dose of ecdysterone per kg body weight BW as applied in other rodent studies, in which ecdysterone caused either hepatic and plasma lipid-lowering effects or antiobesity effects in different rodent models. In order to decipher the potential lipid-lowering actions of ecdysteroids in Zucker rats, measurements of liver and plasma lipid concentrations and hepatic transcriptome analysis was carried out. To further study if ecdysterone is capable of alleviating the strong lipid-synthetic activity in the liver of obese Zucker rats, the study included also two groups of lean Zucker rats which also received either the ecdysterone-supplemented or the non-supplemented diet.

Project description:Patients with long-duration diabetes develop cardiovascular complications resulting in highly increased mortality and complications which affect the kidneys, eyes and peripheral nerves associated with high morbidity. Among the diabetic complications, damage in the eye, diabetic retinopathy, is the most common microvascular complication of diabetes. Diabetic retinopathy is a leading cause of vision-loss globally. It is characterized by a number of different patho-mechanisms including changes in vascular permeability, capillary degeneration, and finally at a late stage overshooting formation of new blood vessels. This expression analysis focused on the use of different experimental models for Diabetes Mellitus and its complications (for a review see 1: Al-Awar et al: Experimental Diabetes Mellitus in Different Animal Models. J Diabetes Res. 2016; doi: 10.1155/2016/9051426). By that, we wanted to uncover the relative contributions of systemic hyperinsulinaemia and/or hyperglycemia to molecular regulations. The following models have been used: As insulinopenic, hyperglycemic model reflecting Type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p.) were used. Wistar rats without STZ injection served as non-diabetic controls. Male obese ZDF rats (Fa/Fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male lean ZDF rats (Fa/-) served as non-diabetic controls. Male obese ZF rats (Fa/Fa) hyperglycemia were used reflecting euglycemia and severe insulin resistance. Male lean ZF rats (Fa/-) served as controls. ZDF and ZF rats were obtained in two genotypes, obese (genotype fa/fa) and lean littermates (genotype Fa/?). All rats were housed in standard cages under a normal light-dark cycle for 16 weeks. All animals had free access to food and water. ZF and Wistar rats received a standard chow (Ssniff R/M) and ZDF rats received Purina 5008 chow. A group size of n=8 were used for all study groups. Wistar rats were rendered type-1 like hyperglycemic and hypoinsulinemic via a single injection of streptocotocin (STZ, 60mg/kg; i.p.) at 7 weeks of age. Obese ZDF rats (fa/fa) develop spontaneously a type-2 diabetes phenotype with persisting hyperglycemia and transient hyperinsulinemia (hyperglycemic, hypoinsulinemic). Obese ZF rats (fa/fa) develop insulin resistance with permanent hyperinsulinemia without concomitant hyperglycemia and no overt diabetes phenotype. Non STZ treated Wistar rats, lean ZDF littermates (Fa/?), and lean ZF littermates (Fa/?) served as controls. All groups were kept for 12 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays.

Dataset Information

Rosiglitazone effects on kidney gene expression

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets