Omics · study · 2026
BCKDK Protects against Obesity-Induced Cardiac Remodelling and Dysfunction by Modulating Mitochondrial ROS-Driven JNK/p38 MAPK Signaling
Listed in NCBI GEO
Obesity cardiomyopathy (OCM), characterized by diastolic dysfunction, often progresses to obese heart failure with preserved ejection fraction and remains a major clinical challenge.
Description
Accumulating evidence indicates that impaired branched-chain amino acid (BCAA) catabolism is present in OCM, and systemic enhancement of BCAA catabolism through global inhibition of branched-chain ketoacid dehydrogenase kinase (BCKDK), a key negative regulator of BCAA oxidation, alleviates cardiac dysfunction.
However, whether cardiac-restricted manipulation of BCAA catabolism is sufficient to confer therapeutic benefits remains unknown. Here, we generated an inducible cardiomyocyte-specific BCKDK knockout mouse model to enhance cardiac BCAA catabolism. Unexpectedly, this model fails to improve and instead exacerbates cardiac dysfunction and ventricular remodelling in OCM.
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Notably, cardiac BCKDK expression is reduced in both OCM mice and obese patients. Cardiomyocyte-specific BCKDK overexpression robustly improves cardiac function and pathological remodelling in OCM, accompanied by further lowering myocardial BCAA levels. Bulk-RNA sequencing and untargeted metabolomics reveal that the cardiomyocyte-specific BCKDK overexpression restore mitochondrial respiratory function and suppress MAPK-driven inflammatory response.
Overall, these findings uncover an unanticipated BCAA-independent role of BCKDK in maintaining cardiomyocyte mitochondrial function and restraining inflammatory signalling, positioning BCKDK as a promising therapeutic target for OCM.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317489 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317489 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1413903 ncbi.nlm.nih.gov/bioproject/PRJNA1413903 ↗
project · from NCBI GEO
- PubMed 42320265 pubmed.ncbi.nlm.nih.gov/42320265 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cardiac remodeling 65% · Cardiomyopathy 75% · Heart 75% · Sequencing 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE317489 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:cardiac-remodeling | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[disease].local:disease:cardiomyopathy | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |