Omics · study · 2026
CCR1 deficiency promotes adipocyte browning via cAMP/PKA/CREB signaling to suppress obesity in mice
Listed in NCBI GEO
Enhancing brown adipose tissue (BAT) activity and browning of white adipose tissue (WAT) are promising novel strategies for combating obesity and insulin resistance.
Description
Previously, we identified CCR1 as a key regulator of non-alcoholic steatosis. Here, we present evidence of the physiological role of CCR1 in obesity and energy homeostasis.
Analysis of Ccr1-/- mice fed a high-fat diet (HFD) revealed inguinal WAT browning, increased BAT activation and brown-mediated genes expression, elevated whole-body energy expenditure, ameliorated macrophage homeostasis, decreased inflammation, and eventually attenuated insulin resistance and obesity. Moreover, Ccr1 deficiency increased adaptive thermogenesis under cold conditions. These phenotypes were also identified in HFD-fed mice treated with BX471, a CCR1 selective inhibitor.
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Mechanistically, Ccr1 knockout elevated WAT cyclic adenosine 3',5'-monophosphate (cAMP) levels, activating cAMP-dependent protein kinase (PKA) and its downstream transcription factor cAMP response element-binding protein, CREB. Overall, Ccr1 deficiency increases BAT activation and WAT browning through the cAMP-related PKA/CREB pathway, thereby preventing obesity and insulin resistance. In addition, CCR1 inhibition by BX471 protects against obesity.
These findings shed light on novel strategies for the treatment of obesity and related diseases.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE274nnn/GSE274417 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE274417 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1146384 ncbi.nlm.nih.gov/bioproject/PRJNA1146384 ↗
project · from NCBI GEO
- PubMed 42557944 pubmed.ncbi.nlm.nih.gov/42557944 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE274417 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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 |