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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

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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.

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

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

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

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2021-08-24 | GSE148894 | GEO

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

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2012-05-30 | GSE38138 | GEO

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2023-06-01 | GSE220864 | GEO

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