Omics · study · 2026
Gut microbiota-glycine-UCP3 axis modulates the protection of canagliflozin against cardiac hypertrophy
Listed in NCBI GEO
Canagliflozin (CANA), a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, exert cardioprotective effects and improve long-term clinical outcomes in heart failure patients without diabetes.
Description
However, given negligible myocardial SGLT2 expression, the mechanisms remain unclear. Here, we found that CANA altered the community structure of gut microbiota in mice subjected to pressure overload.
Moreover, mice receiving microbiota transplants from TAC and CANA-treated mice exhibited better cardiac function compared to those receiving microbiota transplants from TAC-treated donors. Metabolite profiling identified glycine as a key mediator that protected against cardiac hypertrophy in mice. Importantly, the reduced glycine levels in hypertrophic mice were prevented by CANA treatment.
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We further demonstrated that Clostridium sp. was responsible for the degradation of glycine. Mechanistically, we showed that glycine activated the AMP-activated protein kinase α (AMPKα)/ peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway, thus upregulating uncoupling protein 3 (UCP3) to preserve mitochondrial integrity and promote oxidative phosphorylation. UCP3 deficiency largely abolished the protective effect of CANA or glycine treatment against heart failure in mice.
Our findings establish the gut microbiota-derived glycine/UCP3 signaling axis as a novel mechanism through which CANA exerts its anti-hypertrophic effects.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347125 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347125 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1524355 ncbi.nlm.nih.gov/bioproject/PRJNA1524355 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Heart 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE347125 | 12 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[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[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 |