Genetic regulator of mitochondrial metabolism and insulin resistance [RNA-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA680321 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13114586_1.fastq.gz | Fastqsanger.gz | |||
| SRR13114586_2.fastq.gz | Fastqsanger.gz | |||
| SRR13114587_1.fastq.gz | Fastqsanger.gz | |||
| SRR13114587_2.fastq.gz | Fastqsanger.gz | |||
| SRR13114588_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Genetic regulator of mitochondrial metabolism and insulin resistance
| PRJNA680312 | ENA
Project description:Genetic regulator of mitochondrial metabolism and insulin resistance [ncRNA-Seq]
| PRJNA680249 | ENA
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: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:This SuperSeries is composed of the SubSeries listed below.
2021-09-24 | GSE162021 | GEO
Project description:A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a novel role in the control of apoptosis, metabolism and mitochondrial function.
2019-02-25 | GSE110574 | 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:FoxK1/2 – New Components in Insulin Regulation of Cellular and Mitochondrial Metabolism
| PRJNA434000 | ENA
Project description:Purpose: To reveal the mechanism of mitochondrial DNA methylation in the progression of fatty liver and insulin resistance. Methods: Liver mitochondrial DNA bisulfite-sequencing of high-fat diet (HFD) and db/db diabetic mice were using Illumina 4000. Western blot, real-time PCR and confocal microscopy were used for further biochemical validation. Results: In the present study, we found increased mitochondrial localization of DNA methyltransferase 1 (DNMT1) in the liver of high-fat diet (HFD) and db/db diabetic mice. Whole genome bisulfite sequencing of mouse liver mtDNA revealed significant increase of cytosine methylation frequencies including CG, CHG and CHH on both L and H-strand in the diabetic mice comparing with normal control, and ND6 showed the most dramatic increase on the L-strand. Conclusions: Our present study suggests an epigenetic regulatory of mitochondrial homeostasis and insulin sensitivity by DNMT1, providing novel therapeutic targets for the prevention and treatment of fatty liver and type 2 diabetes.
2021-03-27 | GSE111996 | GEO
Project description:During obesity, adipose tissue macrophages (ATM) colonize the white adipose tissue (WAT), where they adapt inflammatory and metabolically activated phenotypes. Here, we demonstrate that COMMD10 is a key regulator of macrophage oxidative capacity in response to chronic caloric excess. Mice with COMMD10-deficiency targeted to macrophages were fed with high-fat-diet (HFD) for 12 weeks. They gained less weight despite similar food intake, and showed improved systemic metabolic indices, sustained adipose tissue insulin sensitivity, increased lipolysis and reduced adipocyte hypertrophy and liver steatosis. COMMD10-deficient ATM directly improved insulin sensitivity and increase lipolysis in co-cultured adipocytes. COMMD10-deficient ATM exhibited increased oxidative respiration and mitochondrial membrane potential after short term (five weeks) and chronic (12 weeks) HFD. Their oxidative respiration was fueled by both glucose and lipids. They better adapted to mitochondrial activation by upregulating NRF2-dependent antioxidant transcriptional module. their increase in mitochondrial activity was furthered supported by COMMD10 modulation of cellular copper-iron balance and interaction with various oxidative phosphorylation related proteins. Our study illuminates COMMD10 as a pivotal regulator of mitochondrial energy production in ATM during constant energy surplus.
2024-11-30 | GSE247350 | GEO