Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bezafibrate reduces the elevated hepatic fumarate level in insulin-deficient streptozotocin mice [visceral adipose tissue]

ABSTRACT: In addition to high intracellular glucose level, the diabetic state is also characterized by altered metabolites, which are pivotal regulators of glucotoxic pathways. In this study we analyzed Bezafibrate (BEZ) treated Streptozotocin (STZ) mice, which showed improved glucose metabolism compared to untreated STZ controls. In order to identify the key molecules and pathways, which participate in the beneficial effects of BEZ, we analyzed the skeletal muscle, white adipose tissue (WAT) and liver samples of BEZ-treated mice using non-targeted metabolomics (NMR spectroscopy), targeted metabolomics (mass spectrometry), microarrays and enzyme activity measurements with a particular focus on the liver. The analysis of muscle and WAT demonstrated that BEZ improved the expressions of genes and levels of metabolites, which could partly regulate the beneficial effects of BEZ on the glucose metabolism. Furthermore, in the liver, BEZ treatment reduced the elevated hepatic fumarate level of STZ mice, which was accompanied by a decreased expression of urea cycle genes. Since the urea cycle is involved in the production of fumarate, which is shown to be participated in glucotoxic pathways, our data suggest that BEZ could attenuate the urea cycle, reduce fumarate level and in turn ameliorate glucotoxicity in the liver of STZ mice

ORGANISM(S): Mus musculus

PROVIDER: GSE179717 | GEO | 2022/03/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Bezafibrate reduces the elevated hepatic fumarate level in insulin-deficient streptozotocin mice [skeletal muscle tissue]

Project description:In addition to high intracellular glucose level, the diabetic state is also characterized by altered metabolites, which are pivotal regulators of glucotoxic pathways. In this study we analyzed Bezafibrate (BEZ) treated Streptozotocin (STZ) mice, which showed improved glucose metabolism compared to untreated STZ controls. In order to identify the key molecules and pathways, which participate in the beneficial effects of BEZ, we analyzed the skeletal muscle, white adipose tissue (WAT) and liver samples of BEZ-treated mice using non-targeted metabolomics (NMR spectroscopy), targeted metabolomics (mass spectrometry), microarrays and enzyme activity measurements with a particular focus on the liver. The analysis of muscle and WAT demonstrated that BEZ improved the expressions of genes and levels of metabolites, which could partly regulate the beneficial effects of BEZ on the glucose metabolism. Furthermore, in the liver, BEZ treatment reduced the elevated hepatic fumarate level of STZ mice, which was accompanied by a decreased expression of urea cycle genes. Since the urea cycle is involved in the production of fumarate, which is shown to be participated in glucotoxic pathways, our data suggest that BEZ could attenuate the urea cycle, reduce fumarate level and in turn ameliorate glucotoxicity in the liver of STZ mice

2022-03-08 | GSE179718 | GEO

Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-treated diabetic mice

Project description:Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), is generally used to treat hyperlipidemia. Clinical trials on patients suffering from type 2 diabetes indicated that BEZ also has beneficial effects on glucose metabolism, but the underlying mechanisms remain elusive. Much less is known about the function of BEZ in type 1 diabetes. Here, we show that BEZ treatment markedly improves hyperglycemia, glucose and insulin tolerance in streptozotocin (STZ)-treated mice, an insulin-deficient mouse model of type 1 diabetes presenting with very high blood glucose levels. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Our data demonstrate a beneficial effect of BEZ treatment on STZ mice reducing diabetes and suggest that BEZ ameliorates impaired glucose metabolism possibly via augmented hepatic mitochondrial performance, improved insulin sensitivity and metabolic flexibility. We performed gene expression microarray analysis on liver tissue derived from streptozotocin-treated mice treated with bezafibrate in addition.

2016-06-29 | E-GEOD-79008 | biostudies-arrayexpress

Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-treated diabetic mice

2016-06-29 | GSE79008 | GEO

Microarray expression analysis of Aquaporin-9 (AQP9) knockout effect in fasted C57Bl/6 mice

Project description:Aquaporin-9 is a glycerol, urea and hydrogen peroxide channel, with highest expression in the liver. We have previously demonstrated that AQP9 is required for hepatocyte glycerol uptake and thus for gluconeogenesis from glycerol. AQP9 gene deletion in db/db mice of the C57BLKS background results in improved glycemia, while glycemia in normal mice is unaffected even during starvation, when glycerol is an important gluconeogenic substrate. To identify mechanisms that compensate the lack of glycerol uptake for gluconeogenesis, we performed a gene expression profiling and metabolomics study.

2021-12-06 | E-MTAB-5849 | biostudies-arrayexpress

Glutaminase 2 Knockdown Reduces Hyperammonemia and Associated Lethality of Urea Cycle Disorder Mouse Model

Project description:Urea cycle disorders with hyperammonemia remain difficult to treat and eventually necessitate liver transplantation. An ornithine transcarbamylase defect (Otcspf-ash) mouse model, a model of urea cycle disorder, was used to test whether knockdown of a key glutamine metabolism enzyme glutaminase 2 (Gls2) or glutamine dehydrogenase 1 (Glud1) could rescue the hyperammonemia and associated lethality induced by a high protein diet. Reduced hepatic expression of Gls2, but not Glud1, by AAV8-mediated delivery of a short hairpin RNA in Otcspf-ash mice diminished hyperammonemia, reduced body weight loss, and reduced lethality. These data suggest that Gls2 hepatic knockdown could help alleviate risk for hyperammonemia and other clinical manifestations of patients suffering from defects in the urea cycle.

2022-06-07 | GSE179342 | GEO

1H NMR metabolomic and transcriptomic analyses reveal urinary metabolites as biomarker candidates in response to protein undernutrition in adult rats

Project description:1H NMR metabolomics was performed on urine samples weekly and on plasma and liver samples collected at week 4 from these animals, to identify metabolites that respond to protein undernutrition. To further investigate metabolites which were fluctuated in response to protein undernutrition in terms of metabolic enzymes, hepatic mRNA microarray and quantitative PCR analyses were also performed at week 4.

2020-01-25 | GSE144207 | GEO

Hepatic gene expression in streptozotocin-induced diabetic mice fed a quercetin diet

Project description:Quercetin is a food component that may ameliorate the diabetic symptoms. We examined hepatic gene expression of BALB/c mice with streptozotocin (STZ)-induced diabetes to elucidate the mechanism of the protective effect of dietary quercetin on diabetes-associated liver injury. We fed STZ-induced diabetic mice with diets containing 0.1% or 0.5% quercetin for 2 weeks and compared the patterns of hepatic gene expression in these groups of mice using a DNA microarray. Diets containing 0.1% or 0.5% quercetin lowered the STZ-induced increase in blood glucose levels and improved plasma insulin levels. A cluster analysis of the hepatic gene expressions showed that 0.5% quercetin diet suppressed STZ-induced alteration of gene expression. Gene set enrichment analysis (GSEA) and quantitative RT-PCR analysis showed that the quercetin diets had their greatest suppressive effect on the STZ-induced elevation of expression of cyclin dependent kinase inhibitor p21(WAF1/Cip1) (Cdkn1a). Six-week-old male mice were divided into 4 groups of 6 mice each, housed in groups of 3 per cage. After 1 week mice were intraperitoneally injected with STZ. Mice (n=6) in the untreated control group did not receive any treatment. After 1 week, 18 mice showing non-fasting blood glucose levels of 230-400 mg/dL were divided into 3 groups: one group was fed with AIN93G only (control group), the others with an AIN93G diet containing 0.1% or 0.5% quercetin (Funakoshi, Tokyo, Japan) for 2 weeks.

2012-05-22 | E-GEOD-38067 | biostudies-arrayexpress

Notum promotes thermogenesis and protects against diet-induced obesity and insulin resistance in mice

Project description:Notum is a liver-secreted inhibitor of Wnt signaling pathway, which protected against diet induced obesity and improved glucose homeostasis when overexpressed in the mouse liver. Adeno-associated virus (AAV) vectors were used to overexpress green fluorescent protein (GFP) or Notum in the livers of male C57BL/6J mice maintained on a chow diet. Four weeks after the AAV injection, inguinal white adipose tissue (WAT) of these mice were collected to study Notum’s effect on gene expression. RNA-seq analysis of inguinal WAT collected from these mice revealed a highly significant enrichment of extracellular matrix (ECM) gene set among the down-regulated genes in the AAV-Notum group as compared to the AAV-GFP group. These data suggest that Notum inhibits WAT fibrosis, which may be one of the mechanisms by which Notum improves glucose homeostasis.

2021-08-24 | GSE148894 | GEO

mRNA therapy restores ureagenesis and corrects glutathione metabolism in argininosuccinic aciduria

Project description:Argininosuccinate lyase (ASL) is a key enzyme integral to the hepatic urea cycle which is required for ammonia detoxification, and the citrulline-nitric oxide (NO) cycle for NO production. ASL deficient patients present with argininosuccinic aciduria (ASA), an inherited metabolic disease with hyperammonaemia and a chronic systemic phenotype with neurocognitive impairment and chronic liver disease. ASL deficiency as an inherited model of systemic NO deficiency, shows enhanced nitrosative and oxidative stress. Here, we describe the dysregulation of glutathione biosynthesis and upstream cysteine utilization in ASL-deficient patients and mice using targeted metabolomics and in vivo positron emission tomography (PET) imaging using (S)-4-(3-18F-fluoropropyl)-L-glutamate ([18F]FSPG). Upregulation of cysteine metabolism contrasted with glutathione depletion and down-regulated antioxidant pathways. hASL mRNA encapsulated in lipid nanoparticles corrected and rescued the neonatal and adult Asl-deficient mouse phenotypes, respectively, enhancing ureagenesis and glutathione metabolism and ameliorating chronic liver disease. We further present [18F]FSPG PET as a novel non-invasive diagnostic tool to assess liver disease and therapeutic efficacy in ASA. These findings support clinical translation of mRNA therapy for ASA.

2023-01-31 | GSE222874 | GEO

Reprogramming of rhythmic liver metabolism by intestine clock

Project description:To assess potential impact of intestine clock on the rhythmicity of peripheral tissues (liver, kidney and WAT), mice with Bmal1 specifically deleted in the intestine (Bmal1-iKO mice, showing loss of clock function in the intestine) were generated. We collected liver, kidney and WAT samples from Bmal1-iKO and control (Bmal1-flox) mice every 4 hours throughout a light/dark cycle, and subsequently performed transcriptomic analyses.

2023-06-01 | GSE220864 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data