Zucker diabetic fatty (ZDF)/Zucker lean control (ZLC) comparisons
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE1080 | GEO | 2004/03/01
SECONDARY ACCESSION(S): PRJNA87181
REPOSITORIES: GEO
Similar Datasets
Project description:Type 2 diabetes differs from type 1 diabetes in its pathogenesis. Type 1 diabetic diaphragm has altered gene expression which includes lipid and carbohydrate metabolism, ubiquitination and oxidoreductase activity. The objectives of the present study were to assess respiratory muscle gene expression changes in type 2 diabetes and to determine whether they are greater for the diaphragm than an upper airway muscle. Diaphragm and sternohyoid muscle from Zucker diabetic fatty (ZDF) rats were analyzed with Affymetrix gene expression arrays. The two muscles had 97 and 102 genes, respectively, with at least ±1.5-fold significantly changed expression with diabetes, and these were assigned to gene ontology groups based on over-representation analysis. Several significantly changed groups were common to both muscles, including lipid metabolism, carbohydrate metabolism, muscle contraction, ion transport and collagen, although the number of genes and the specific genes involved differed considerably for the two muscles. In both muscles there was a shift in metabolism gene expression from carbohydrate metabolism toward lipid metabolism, but the shift was greater and involved more genes in diabetic diaphragm than diabetic sternohyoid muscle. Groups present in only diaphragm were blood circulation and oxidoreductase activity. Groups present in only sternohyoid were immune & inflammation and response to stress & wounding, with complement genes being a prominent component. In conclusion, type 2 diabetes-induced gene expression changes in respiratory muscles has both similarities and differences relative to previous data on type 1 diabetes gene expression. Furthermore, the diabetic alterations in gene expression differ between diaphragm and sternohyoid. 18-week-old Zucker diabetic fatty rats: 6 normal and 5 diabetic diaphragms and sternohyoids.
2014-05-12 | E-GEOD-21791 | biostudies-arrayexpress
Project description:Here we analyzed how whole egg consumption in Zucker Diabetic Fatty (ZDF) rats alters microRNA and mRNA expression across the adipose, liver, kidney, and prefrontal cortex tissue. Male ZDF (fa/fa) rats (n = 12) and their lean controls (fa/+) (n = 12) were obtained at 6 wk of age. Rats had ad libitum access to water and were randomly assigned to a modified semi-purified AIN93G casein-based diet or a whole egg-based diet, both providing 20% protein (w/w). TotalRNA libraries were prepared using QuantSeq 3' mRNA-Seq and Lexogen smallRNA library prep kits and were further sequenced on an Illumina HighSeq3000. Differential gene expression was conducted using DESeq2 in R and Benjamini-Hochberg adjusted P- values controlling for false discovery rate at 5%.We identified 9 microRNAs and 583 genes that were differentially expressed in response to 8 wk of consuming whole egg-based diets.
2020-09-05 | GSE157491 | GEO
Project description:Type 2 diabetes differs from type 1 diabetes in its pathogenesis. Type 1 diabetic diaphragm has altered gene expression which includes lipid and carbohydrate metabolism, ubiquitination and oxidoreductase activity. The objectives of the present study were to assess respiratory muscle gene expression changes in type 2 diabetes and to determine whether they are greater for the diaphragm than an upper airway muscle. Diaphragm and sternohyoid muscle from Zucker diabetic fatty (ZDF) rats were analyzed with Affymetrix gene expression arrays. The two muscles had 97 and 102 genes, respectively, with at least ±1.5-fold significantly changed expression with diabetes, and these were assigned to gene ontology groups based on over-representation analysis. Several significantly changed groups were common to both muscles, including lipid metabolism, carbohydrate metabolism, muscle contraction, ion transport and collagen, although the number of genes and the specific genes involved differed considerably for the two muscles. In both muscles there was a shift in metabolism gene expression from carbohydrate metabolism toward lipid metabolism, but the shift was greater and involved more genes in diabetic diaphragm than diabetic sternohyoid muscle. Groups present in only diaphragm were blood circulation and oxidoreductase activity. Groups present in only sternohyoid were immune & inflammation and response to stress & wounding, with complement genes being a prominent component. In conclusion, type 2 diabetes-induced gene expression changes in respiratory muscles has both similarities and differences relative to previous data on type 1 diabetes gene expression. Furthermore, the diabetic alterations in gene expression differ between diaphragm and sternohyoid.
2014-05-12 | GSE21791 | GEO
Project description:Colesevelam is a bile acid sequestrant approved to treat both hyperlipidemia and type 2 diabetes, but the mechanism for its glucose lowering effects is not fully understood. The aim of this study was to investigate the role of hepatic microRNA’s as regulators of metabolic disease and to investigate the link between the cholesterol and glucose lowering effects of colesevelam. To quantify the impact of colesevelam treatment in rodent models of diabetes, metabolic studies were performed in Zucker Diabetic Fatty (ZDF) rats and db/db mice. Colesevelam treatments significantly decreased plasma glucose levels and increased glycolysis in the absence of changes to insulin levels in ZDF rats and db/db mice. High-throughput sequencing and real-time PCR were used to quantify hepatic miRNA and mRNA changes, and the cholesterol-sensitive miR-96/182/183 cluster was found to be significantly increased in livers from ZDF rats treated with colesevelam compared to vehicle controls. In summary, these results support that colesevelam likely improves glycemic control through hepatic miR-96/182/183, a mechanism that directly links cholesterol and glucose metabolism.
2018-07-10 | GSE116826 | GEO
Project description:Endurance exercise training has been shown to decrease whole-body and skeletal muscle insulin resistance and increase glucose tolerance in conditions of both pre-diabetes and overt type 2 diabetes. However, the adaptive responses in skeletal muscle at the molecular and genetic level for these beneficial effects of exercise training have not been clearly established in an animal model of pre-diabetes. The present study identifies alterations in skeletal muscle gene expression that occur with exercise training in pre-diabetic, insulin-resistant obese Zucker (fa/fa) rats and insulin-sensitive lean Zucker (Fa/-) rats. Treadmill running for up to 4 weeks caused significant enhancements of glucose tolerance as assessed by the integrated area under the curve for glucose (AUCg) during an oral glucose tolerance test in both lean and obese animals. Using microarray analysis, a set of only 12 genes was identified as both significantly altered (>1.5-fold change relative to sedentary controls; p<0.05) and significantly correlated (p<0.05) with the AUCg. Two of these genes, peroxisome proliferator-activated receptor-g coactivator 1a (PGC-1a) and the z-isoform of protein kinase C (PKC-z), have known involvement in the regulation of skeletal muscle glucose transport. We confirmed that protein expression levels of PGC-1a and PKC-z were positively correlated with the mRNA expression levels for these two genes. Overall, this study has identified a limited number of genes in soleus muscle of lean and obese Zucker rats that are associated with decreased insulin resistance and increase glucose tolerance following endurance exercise training. These findings could guide the development of pharmaceutical M-^Sexercise mimeticsM-^T in the treatment of insulin-resistant, pre-diabetic or overtly type 2 diabetic individuals.
2009-11-16 | E-TABM-213 | biostudies-arrayexpress
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 (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). 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.
2008-04-06 | E-GEOD-7193 | biostudies-arrayexpress
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.
2021-03-07 | GSE168390 | GEO
Project description:We used Affymetrix microarrays to investigate gene expression changes in the liver of lean female Zucker rats exposed to a normal diet supplemented with a rosemary extract rich in the diterpenic compound, carnosic acid (CA). The aim of this work was to determine whether the daily intake (with the standard diet) of the rosemary extract (RE) enriched in CA (40%) for 64 days exerted any modulatory effects, at the level of gene expression, in the liver of lean Zucker female rats. Female lean Zucker rats were randomly assigned to two experimental groups (n= 7 animals per group) as follows: (1) control group, fed a standard diet (CT); (2) treated group, fed a standard diet supplemented (0.05% w/w) with the RE rich in CA (RE). At the end of the experimental procedure (64 days), total RNA was extracted from the liver to compare differential gene expression between the two groups. Liver differential gene expression after 64 days of supplementation between the CT group and the RE group (effects of the extract supplementation).
2013-09-15 | E-GEOD-48373 | biostudies-arrayexpress
Project description:We used Affymetrix microarrays to investigate gene expression changes in the liver of lean female Zucker rats exposed to a normal diet supplemented with a rosemary extract rich in the diterpenic compound, carnosic acid (CA).
2013-09-15 | GSE48373 | GEO
Project description:Population based studies have established that androgen deficiency in males correlates with type 2 diabetes, visceral adiposity, and metabolic syndrome. Androgen therapy has been investigated as a possible treatment regime to combat these disorders. However, the molecular mechanism of androgen effects on these diseases still remain poorly understood. The zucker diabetic fatty (ZDF) rat, containing a mutation in the leptin receptor, is a well-investigated model of obesity and type 2 diabetes. Male rats are characterized as androgen deficient and spontaneously develop obese, hyperlipidemia, hyperglycemia and hyperinsulinemia. In this study, we used ZDF male rats as a model of metabolic syndrome to investigate the effects of testosterone administration on the development of the metabolic conditions. Methods: Male ZDF rats at six week of age were randomly divided into two groups and administered testosterone undecanoate(TU) or vehicle alone every three days for three weeks. After three weeks, overnight fasted blood glucose and insulin concentrations were significantly higher and glucose tolerance and insulin sensitivity were impaired in TU treated ZDF rats compared to vehicle controls. Moreover, increased serum triglycerides and VLDL were observed in TU treated rats. To further explore the observed metabolic changes in TU treated ZDF rats, whole-genome microarray analysis were performed on isolated liver mRNA. Results: Array analysis revealed that many hepatic lipogenic genes were increased in male ZDF rat livers treated with TU. Interestingly, SREBP-1c, a key transcriptional activator of lipogenic genes and PGC-1 , an activator of SREBP-1c were induced while small heterodimer partner, a transcriptional inhibitor of lipogenic genes was suppressed by TU treatment. Exploring signaling pathways for these effects, we observed that the hepatic activated forms of STAT3 and AMPK, two known inhibitors of hepatic lipogenesis, were decreased in TU treated rat. Moreover, we observed that DHT could block the induction of STAT3 and AMPK phosphorylation in treated primary human hepatocytes. Preliminarily, in the leptin receptor positive zucker diabetic lean male rats, we observed that TU treatment has an oppose effect on the hepatic lipogenic genes, suggesting that hepatic leptin signaling may influence androgen signaling. Further insight into the relationship between androgen deficiency and the leptin system may help improve treatment of the metabolic syndrome. Population based studies have established that androgen deficiency in males correlates with type 2 diabetes, visceral adiposity, and metabolic syndrome. Androgen therapy has been investigated as a possible treatment regime to combat these disorders. However, the molecular mechanism of androgen effects on these diseases still remain poorly understood. The zucker diabetic fatty (ZDF) rat, containing a mutation in the leptin receptor, is a well-investigated model of obesity and type 2 diabetes. Male rats are characterized as androgen deficient and spontaneously develop obese, hyperlipidemia, hyperglycemia and hyperinsulinemia. In this study, we used ZDF male rats as a model of metabolic syndrome to investigate the effects of testosterone administration on the development of the metabolic conditions. Two-condition experiment. (1) lean ZDF rats (control) vs. lean ZDF rats (testosterone treated). (2) obese ZDF rats (control) vs. obese ZDF rats (testosterone treated). Biological replicates: 4 control replicates, 4 treated replicates.
2012-09-02 | E-GEOD-23941 | biostudies-arrayexpress