Text · study · 2026
Ethanol reshapes FFC-driven steatohepatitis through time-dependent fibrosis and lipid-droplet remodeling
Listed in NCBI GEO
Metabolic dysfunction and alcohol exposure drive steatotic liver disease, yet how ethanol intersects with metabolic steatohepatitis remains incompletely defined.
Description
Our iterative model examined how ethanol ingestion alters high-fat, -fructose, and -cholesterol (FFC)-driven liver injury, identifying MetALD-relevant features. A pilot study in male and female C57BL/6J mice compared chow diet (CD), FFC, CD+ethanol (E), and FFC+E on high-glucose/fructose (sugar) water (SW) at 6, 16, and 24 weeks.
A redesigned study lowered glucose/fructose exposure, modified ethanol acclimation, and tested five male cohorts, CD, CD+SW, FFC+SW, CD+SW+E, FFC+SW+E, at 16 and 24 weeks. In the pilot study, FFC-dominant hepatomegaly, aminotransferase elevation, steatosis, chemokine induction, and fibrosis, without additive ethanol effects were observed. In the redesigned model, FFC drove weight gain, hepatomegaly, steatosis, aminotransferase elevation, and Ccl2/Timp1-associated fibroinflammatory remodeling.
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However, ethanol selectively modified progression of fibrosis and lipid droplets. At 16 weeks, FFC+SW+E increased collagen area compared with FFC+SW despite lower body/liver mass and no additive aminotransferase response. Morphometry showed enlarged lipid droplets in both FFC groups, but FFC/ethanol demonstrated reduced lipid droplet area.
In contrast, hepatic triglycerides increased with FFC but did not differ between FFC+SW and FFC+SW+E, supporting altered lipid-storage architecture rather than lipid accumulation or steatosis. Ccxl1 was induced by ethanol in CD mice but not uniformly upregulated on FFC. By 24 weeks, fibrosis, αSma staining, qPCR markers, and NanoString immune profiles converged between FFC groups.
Thus, chronic ethanol in a MetALD mouse model modifies selected temporal, lipid-storage, and inflammatory features of FFC-driven liver injury rather than uniformly intensifying disease.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337144 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337144 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1484129 ncbi.nlm.nih.gov/bioproject/PRJNA1484129 ↗
project · from NCBI GEO
- PubMed 42631413 pubmed.ncbi.nlm.nih.gov/42631413 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by array · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE337144 | 7 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | 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-array | 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 |