Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-6210
PROVIDER: PRJNA100627 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Objective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range. Results: High-fat diet (HFD) caused insulin resistance and severe hepatic lipid accumulation, but respiratory chain parameters were unchanged. Livers from insulin-resistant IR/IRS-1+/- mice had normal lipid contents and normal respiratory chain parameters, however showed mitochondrial uncoupling. Livers from severely hyperglycemic and hypoinsulimic, streptozotocin (STZ)-treated mice had massively depleted lipid levels, but respiratory chain abundance was unchanged. However, their mitochondria showed increased abundance and activity of the respiratory chain, which was better coupled compared to controls. Conclusions: Insulin resistance, either induced by obesity or by genetic manipulation, does not cause mitochondrial dysfunction in the liver of mice. However, severe insulin deficiency and high blood glucose levels in mice cause an enhanced performance of the respiratory chain, probably in order to maintain the high energy requirement of the unsuppressed gluconeogenesis. We performed gene expression microarray analysis on liver tissue derived from mice treated with STZ or standard diet (control).
2013-12-10 | E-GEOD-39752 | biostudies-arrayexpress
Project description:Mitochondrial energy metabolism and function are key processes underlying the pathophysiology of insulin resistance and predisposition to type 2 diabetes. This is because mitochondria produce most of the energy required by the cell. Impaired energy production, use of energy stores and mitochondrial dysfunction are major features in metabolic diseases. Nevertheless, it remains uncertain how mitochondrial dysfunction can cause, contribute to, or result in insulin resistance and metabolic diseases. Furthermore there is growing evidence from genetic and genome wide-association studies that genetic variation in mtDNA contributes to these common metabolic diseases (Wallace, 2005), however there has been essentially no in vivo functional validation for these findings. Therefore we generated a mouse model homozygous for a polymorphism in the Mrpp3 gene identified in the French Canadian population responsible for 22% of mitochondrial epitranscriptome variation, with likely consequences on metabolism. We investigated the in vivo effects of the polymorphism on mitochondrial function and metabolism in mice fed normal and high fat diet. We identify that the polymorphism reduces the efficiency of mitochondrial RNA processing and this is most pronounced in the pancreas that results in insulin resistance. The MRPP3 protein containing the Asn434Ser polymorphism associates specifically with the calcium antiporter LETM1 preventing effective release of calcium from mitochondria and consequently impairs insulin release from the pancreatic islet cells of these mice. Reduction in insulin secretion and enlarged pancreatic islet size results in lower circulating levels of insulin that causes insulin resistance and liver steatosis. Our findings reveal for the first time the link between mitochondrial gene regulation and insulin resistance via calcium signaling.
2021-09-24 | GSE162020 | GEO
Project description:Mitochondrial energy metabolism and function are key processes underlying the pathophysiology of insulin resistance and predisposition to type 2 diabetes. This is because mitochondria produce most of the energy required by the cell. Impaired energy production, use of energy stores and mitochondrial dysfunction are major features in metabolic diseases. Nevertheless, it remains uncertain how mitochondrial dysfunction can cause, contribute to, or result in insulin resistance and metabolic diseases. Furthermore there is growing evidence from genetic and genome wide-association studies that genetic variation in mtDNA contributes to these common metabolic diseases (Wallace, 2005), however there has been essentially no in vivo functional validation for these findings. Therefore we generated a mouse model homozygous for a polymorphism in the Mrpp3 gene identified in the French Canadian population responsible for 22% of mitochondrial epitranscriptome variation, with likely consequences on metabolism. We investigated the in vivo effects of the polymorphism on mitochondrial function and metabolism in mice fed normal and high fat diet. We identify that the polymorphism reduces the efficiency of mitochondrial RNA processing and this is most pronounced in the pancreas that results in insulin resistance. The MRPP3 protein containing the Asn434Ser polymorphism associates specifically with the calcium antiporter LETM1 preventing effective release of calcium from mitochondria and consequently impairs insulin release from the pancreatic islet cells of these mice. Reduction in insulin secretion and enlarged pancreatic islet size results in lower circulating levels of insulin that causes insulin resistance and liver steatosis. Our findings reveal for the first time the link between mitochondrial gene regulation and insulin resistance via calcium signaling.
2021-09-24 | GSE161978 | GEO
Project description:PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc1beta gene (PGC1beta E3,4-/E3,4- mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERRalpha, a major target of PGC1beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC1beta mutant mice have normal skeletal muscle response to insulin, but have hepatic insulin resistance. These results demonstrate that PGC1beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver. Experiment Overall Design: Gene expression levels in liver tissue and quadriceps muscle were compared between WT/Control and PGC1beta mutant tissue. Total RNA was extracted from liver and skeletal muscle using RNAeasy kit (Qiagen, Valencia, CA), according to the manufacturerâ??s instructions. Synthesis of cRNA, hybridization and scanning of the Affymetrix Murine 430 2.0 chip was performed by Dana Farber Cancer Institute Microarray Core Facility. The microarray data was analyzed by Clustering Analysis using the d-Chip software (Li and Wong, 2001).
2009-04-24 | E-GEOD-6210 | biostudies-arrayexpress
Project description:Objective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range. Results: High-fat diet (HFD) caused insulin resistance and severe hepatic lipid accumulation, but respiratory chain parameters were unchanged. Livers from insulin-resistant IR/IRS-1+/- mice had normal lipid contents and normal respiratory chain parameters, however showed mitochondrial uncoupling. Livers from severely hyperglycemic and hypoinsulimic, streptozotocin (STZ)-treated mice had massively depleted lipid levels, but respiratory chain abundance was unchanged. However, their mitochondria showed increased abundance and activity of the respiratory chain, which was better coupled compared to controls. Conclusions: Insulin resistance, either induced by obesity or by genetic manipulation, does not cause mitochondrial dysfunction in the liver of mice. However, severe insulin deficiency and high blood glucose levels in mice cause an enhanced performance of the respiratory chain, probably in order to maintain the high energy requirement of the unsuppressed gluconeogenesis.
2013-12-10 | GSE39752 | GEO
Project description:PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc1beta gene (PGC1beta E3,4-/E3,4- mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERRalpha, a major target of PGC1beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC1beta mutant mice have normal skeletal muscle response to insulin, but have hepatic insulin resistance. These results demonstrate that PGC1beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver. Keywords: Liver and quadricpes muscle gene expression, WT vs. PGC1beta mutant
2007-01-01 | GSE6210 | GEO
Project description:Adipose Rab10 Knockout Causes Insulin Resistance through Impaired Glucose Uptake
| PRJNA287703 | ENA
Project description:Metabolic responses begin promptly upon the initiation of infection, and progress as a series of coordinated events. Mitochondria may play a key role in the development of insulin resistance. Reduced energy production and mitochondrial dysfunctional may further favor infection, and be an important step in the establishment of chronic and persistent infections. We have used mouse skeletal muscle transcriptome data which have led to the hypothesis that 2-AA causes harm to the host by triggering mitochondrial dysfunction in skeletal muscle. The gastrocnemius muscles were isolated from control and 4days 2-AA treated mouse for RNA extraction and hybridization on Affymetrix microarrays.
2013-01-28 | E-GEOD-43779 | biostudies-arrayexpress
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2021-05-05 | PXD022309 | Pride