Astrocyte-Specific DGAT1 Inhibition to Prevent Lipid Droplet-Induced Neuroinflammation
Curated pathway from expert analysis
flowchart TD
A["DGAT1 Acyltransferase<br/>Diacylglycerol Acyltransferase"]
B["Triglyceride Synthesis<br/>Fatty Acid Incorporation"]
C["LD Formation<br/>Cytosolic Lipid Droplet Biogenesis"]
D["ER Lipid Homeostasis<br/>Membrane Fluidity Maintenance"]
E["DGAT1 Inhibition<br/>Reduced Triglyceride and Improved Insulin"]
F["Lipid Droplet Accumulation<br/>Cellular Lipotoxicity and Stress"]
G["omega-3 PUFA Supplementation<br/>DGAT1 Activity Modulation"]
A --> B
B --> C
C --> D
D --> E
F -.->|"impairs"| D
G -.->|"modulates"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for DGAT1 yet. Search RCSB →
Median TPM across 13 brain regions for DGAT1 from GTEx v10.
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for DGAT1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF astrocytes are treated with a selective DGAT1 inhibitor (AGK-2 at 10μM) for 48 hours, THEN lipid droplet area per astrocyte will decrease by ≥50% AND secretion of inflammatory cytokines (IL-6, TNF- | Astrocytes treated with DGAT1 inhibitor will show reduced lipid droplet accumulation and lower inflammatory cytokine secretion when stimulated with IL-1β (10ng/ | — no observation — | pending | 0.70 |
| IF astrocyte-specific DGAT1 is genetically knocked out using GFAP-Cre;DGAT1-flox mice, THEN lipid droplet burden in hippocampus will be reduced by ≥60% AND microglial activation (Iba1+ area) will be a | Astrocyte-specific DGAT1 knockout mice on high-fat diet will exhibit fewer hippocampal lipid droplets and reduced microglial activation markers. | — no observation — | pending | 0.65 |