Omics · study · 2026
Obesity disrupts CtBP2-mediated maintenance of the transcriptional equilibrium in hypothalamic feeding circuitry [POMC KO]
Listed in NCBI GEO
Feeding behavior, a vital activity in the lives of all captive animals, is orchestrated by a delicate equilibrium between the orexigenic and anorexigenic activities of neurons in the hypothalamus.
Description
This exquisite control of neuropeptides governing the feeding behavior can be a focal point in the pathogenesis of obesity, and unraveling of the intricate transcriptional systems behind this may offer clues to develop approaches for better management of obese subjects.
The transcriptional corepressor, C-terminal binding protein 2 (CtBP2), has been reported to be a metabolite-sensor inactivated in liver tissues and pancreatic β-cells in obesity. Here we describe a transcriptional system regulated by CtBP2 in hypothalamus. Our global mapping of CtBP2 binding sites by ChIP-seq reveals the recruitment of CtBP2 to the promoters of those neuropeptides as well as other key genes involved in the maintenance of hypothalamic neuronal activities.
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Whereas the expression of CtBP2 is not altered in obese mouse models, the recruitment of CtBP2 to the promoters of those neuropeptides is diminished in obesity, suggesting allosteric inactivation of CtBP2 in the metabolic milieu in obesity in this tissue. Exogenous expression of CtBP2 in hypothalamic cells decreases NPY gene promoter activity, and loss of CtBP2 in hypothalamic neurons in mice increases expression levels of orexigenic neuropeptides.
These findings illustrate a sequential event where obesity promotes orexigenic behavior through metabolic inactivation of CtBP2. Our findings underscore a previously unexplored layer within the redundant transcriptional systems that regulate the hypothalamic feeding circuitry.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE266nnn/GSE266966 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266966 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1108859 ncbi.nlm.nih.gov/bioproject/PRJNA1108859 ↗
project · from NCBI GEO
- PubMed 42522895 pubmed.ncbi.nlm.nih.gov/42522895 ↗
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 | GSE266966 | 11 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 |