Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-omics Analysis Unveils Metabolic Inflexibility Manifesting as Impaired Branched Amino Acid and Enhanced Fatty Acid Degradation in a Mouse Model of Diabetic Cardiomyopathy [ATAC-seq]

ABSTRACT: Diabetic cardiomyopathy (DbCM) is an important clinical syndrome of diabetes and cause great burden to the people's life and health. Understanding its intrinsic epigenetic and metabolic alterations is critical to develop drugs for the treatment of DbCM. Multiple omics technology provides a feasible way for parsing the epigenetic characteristics and metabolic signatures associated with DbCM. The heart isolated from Male db/db mice and db/m mice were used for the analysis of high-throughput sequencing. Non-targeted metabolomics and amino acid-targeted metabolomics analyses were performed to detect the metabolites in plasma and heart tissues. Additionally, RNA-seq, proteomics, and ATAC-seq were employed to elucidate the underlying transcriptional-metabolic regulatory network mechanism in DbCM.

ORGANISM(S): Mus musculus

PROVIDER: GSE274499 | GEO | 2025/01/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Multi-omics Analysis Unveils Metabolic Inflexibility Manifesting as Impaired Branched Amino Acid and Enhanced Fatty Acid Degradation in a Mouse Model of Diabetic Cardiomyopathy [RNA-seq]

Project description:Diabetic cardiomyopathy (DbCM) is an important clinical syndrome of diabetes and cause great burden to the people's life and health. Understanding its intrinsic epigenetic and metabolic alterations is critical to develop drugs for the treatment of DbCM. Multiple omics technology provides a feasible way for parsing the epigenetic characteristics and metabolic signatures associated with DbCM. The heart isolated from Male db/db mice and db/m mice were used for the analysis of high-throughput sequencing. Non-targeted metabolomics and amino acid-targeted metabolomics analyses were performed to detect the metabolites in plasma and heart tissues. Additionally, RNA-seq, proteomics, and ATAC-seq were employed to elucidate the underlying transcriptional-metabolic regulatory network mechanism in DbCM.

2025-01-22 | GSE274500 | GEO

Yap regulates fatty acid oxidation in skeletal muscle [ATAC-seq]

Project description:The Hippo signalling pathway effector Yap positively regulates adult skeletal muscle mass. However, the biological processes that are modulated by Yap in skeletal muscle remain elusive. Using an integrated transcriptomics and proteomics approach, we define the transcriptional programme regulated by Yap in adult skeletal muscle and demonstrate that Yap is a regulator of metabolic substrate utilisation. Inhibition of Yap in mammalian skeletal muscle results in increased, but incomplete, oxidation of fatty acids and features of lipotoxicity. In line with these findings, we demonstrate that Yap abundance is reduced in the skeletal musculature of obese db/db mice, and in muscle biopsies from obese, insulin-resistant humans where YAP levels positively correlate with whole-body metabolic flexibility. Increasing Yap abundance in the striated muscle of db/db mice attenuated the accumulation of fat mass and development of hepatic steatosis. Our findings demonstrate a vital role for Yap in skeletal muscle as a mediator of metabolic substrate utilisation. Modulating Yap activity in skeletal muscle warrants consideration as part of comprehensive approaches to treat metabolic disease.

2021-02-18 | GSE144137 | GEO

Yap regulates fatty acid oxidation in skeletal muscle [RNA-seq]

2021-02-18 | GSE144135 | GEO

Integrated multi-omics analysis of adverse cardiac remodeling and metabolic inflexibility upon ErbB2 and ERR⍺ deficiency

Project description:Functional oncogenic links between ErbB2 and ERR⍺ in HER2+ breast cancer patients support a therapeutic benefit of co-targeted therapies. However, ErbB2 and ERR⍺ also play key roles in heart physiology, and this approach could pose a potential liability to cardiovascular health. Using integrated phosphoproteomic, transcriptomic and metabolic profiling, we uncovered molecular mechanisms associated with the adverse remodeling of cardiac functions in mice with combined attenuation of ErbB2 and ERR⍺ activity. Genetic disruption of both effectors results in profound effects on cardiomyocyte architecture, inflammatory response and metabolism, the latter leading to a decrease in fatty acyl-carnitine species further increasing the reliance on glucose as a metabolic fuel, a hallmark of failing hearts. Furthermore, integrated omics signatures of ERR⍺ loss-of-function and doxorubicin treatment exhibit reciprocal features of chemotherapeutic cardiotoxicity. These findings thus reveal potential cardiovascular risks in discrete combination therapies in the treatment of breast and other cancers.

2022-09-19 | GSE199150 | GEO

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Project description:We reported a 28-day Intermittent fasting (IF) regimen improved cognitive deficits in db/db mice via a microbiota-metabolites-brain axis assessed by behavioral tests and multiple-omics analysis (transciptomics, 16S rRNA sequencing and metabolomics). Here we present transcriptomics data of mice hippocampus. A total of 310.85Gb clean RNA-SEQ reads of all mice with an average depth of 3.86x were obtained and were then mapped against the Mus musculus genome to obtain the gene expression FPKM values for each sample. We detected 27,094 genes (including 1,345 new predicted genes with no annotation) with FPKM value. Among them, 1,181 genes were found to be only highly expressed in db/db-IF mice compared to db/db and db/m mice, using Differentially Expressed Genes (DEG) analysis, most of which enriched in mitochondrial-related GO terms. Besides, IF strongly elevated genes related to KEGG pathway of oxidative phosphorylation (OXPHOS) via up-regulating mitochondrial located genes expression. In consistent with results from RNA-sequencing analysis, the qPCR analysis confirmed that mitochondrial and metabolic genes expressed were upregulated by IF in db/db mice. In conclusion, IF regimen significantly enhanced mitochondrial and energy metabolism related genes expressions in diabetic mice hippocampus.

2020-02-01 | GSE125387 | GEO

USP28-regulated mitochondrial homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts [ChIP-seq]

Project description:The majority of diabetics are susceptible to cardiac dysfunction and heart failure, while conventional drug therapy cannot correct diabetic cardiomyopathy (DCM) progression. Herein, we assessed the potential role and therapeutic value of ubiquitin-specific protease 28 (USP28) on the metabolic vulnerability of DCM. PPARα-/- in the db/db background mice were constructed to check the mechanism of USP28 in vivo. Inducible cardiac-specific deletion of Mfn2 in the db/db background mice was utilized to evaluate USP28-mediated cardioprotection. chromatin immunoprecipitation (ChIP) assays revealed that PPARα promote mitofusin 2 (Mfn2) transcription, thereby impeding mitochondrial morphofunctional defects.

2023-10-15 | GSE244905 | GEO

Molecular Mechanism of type 2 diabetes mellitus-mediated heart failure with preserved ejection fraction

Project description:Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with several comorbidities, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-induced cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient db/db homozygous (Lepr db/db) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr db/db mouse hearts. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr db/db heart tissues. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, CAMZYOS (mavacamten, which is a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment (herein after denotes as MYK-461), was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression, suggesting its promise as a therapeutic treatment for HFpEF.

2024-08-01 | GSE235934 | GEO

Transcriptomic study of heart tissue from diabetic cardiomyopathy mice

Project description:To explore the key genes involved in spontaneous diabetic cardiomyopathy, db/db and BKS mice were used to examine the differently expressed genes in the related progresses. Briely, the heart transcriptome of db/db and BKS mice was correlated with the heart function, cardiomyocyte ultrastructure and histopathology characters.

2021-09-24 | GSE161931 | GEO

Integrated multi-omics analysis of adverse cardiac remodeling and metabolic inflexibility upon ErbB2 and ERR⍺ deficiency

2022-09-22 | PXD032766 | Pride

Transcriptome Alteration in the Diabetic Heart by Rosiglitazone: Implications for Cardiovascular Mortality

Project description:The type 2 diabetes medication, rosiglitazone, has come under scrutiny for possibly increasing the risk of cardiac disease and death. To investigate the effects of rosiglitazone on the diabetic heart, we performed cardiac transcriptional profiling of a murine model of type 2 diabetes, the C57BL/KLS-leprdb/leprdb (db/db) mouse. We compared cardiac gene expression profiles from three groups: untreated db/db mice (db-c), db/db mice after rosiglitazone treatment (db-t), and non-diabetic db/+ mice. Mice were divided into three groups: Non-diabetic controls (db/+), untreated diabetic controls (db-c), and rosiglitazone-treated diabetic mice (db-t). Whole-heart RNA from five mice from each of the three groups after four months with or without treatment was used for microarray analysis.Universal Reference RNAs for mouse (Stratagene, La Jolla, CA) were purchased as microarray reference controls.

2012-03-28 | E-GEOD-36875 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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