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Apolipoprotein E Induces Lipid Accumulation Through Dgat2 That Is Prevented with Time-Restricted Feeding in Drosophila
Ruan Carlos Macêdo de Moraes, Jonathan R. Roth, Hailey Mao, Savannah R. Crawley, Brittney P. Xu, John C. Watson, Girish C. Melkani. Genes, 2024-10-25
Topic: Brain proteins, microglia and lab models
We report that pan-neuronal expression of each ApoE allele induces lipid accumulation specifically in the brain, but not in the muscle. However, this was not the case when expressed with muscle-specific drivers. ApoE2- and ApoE3-induced lipid accumulation is dependent on the expression of Dgat2, a key regulator of triacylglycerol production, while ApoE4 still induces lipid accumulation even with knock-down of Dgat2. Additionally, we find that implementation of time-restricted feeding (TRF), a dietary intervention in which food access only occurs in the active period (day), prevents ApoE-induced lipid accumulation in the brain of flies and modulates lipid metabolism genes. Altogether, our results demonstrate that ApoE induces lipid accumulation in the brain, that ApoE4 is unique in causing lipid accumulation independent of Dgat2, and that TRF prevents ApoE-induced lipid accumulation. These results support the idea that lipid metabolism is critical in AD, and that TRF could be a promising therapeutic approach to prevent ApoE-associated dysfunction in lipid metabolism.
Key findings
- We report that pan-neuronal expression of each ApoE allele induces lipid accumulation specifically in the brain, but not in the muscle.
- However, this was not the case when expressed with muscle-specific drivers.
- ApoE2- and ApoE3-induced lipid accumulation is dependent on the expression of Dgat2, a key regulator of triacylglycerol production, while ApoE4 still induces lipid accumulation even with knock-down of Dgat2.
- Additionally, we find that implementation of time-restricted feeding (TRF), a dietary intervention in which food access only occurs in the active period (day), prevents ApoE-induced lipid accumulation in the brain of flies and modulates lipid metabolism genes.
- Altogether, our results demonstrate that ApoE induces lipid accumulation in the brain, that ApoE4 is unique in causing lipid accumulation independent of Dgat2, and that TRF prevents ApoE-induced lipid accumulation.
Why it matters
This study in fruit flies found that different ApoE alleles cause lipid buildup in the brain, with ApoE4 acting independently of Dgat2, and that time-restricted feeding prevented this buildup. It is early animal work and does not test a treatment, cure, or prevention for Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Genes) |
| Journal's citation record | 1 / 4 | Genes: journal h-index 143 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “drosophila”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 1 / 6 | Cited 0.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Girish Chandra Melkani: h-index 21 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Alabama at Birmingham: institution h-index 1,118 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39596576) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
de Moraes, R. C. M., Roth, J. R., Mao, H., Crawley, S. R., Xu, B. P., Watson, J. C., et al. (2024). Apolipoprotein E Induces Lipid Accumulation Through Dgat2 That Is Prevented with Time-Restricted Feeding in Drosophila. Genes. https://doi.org/10.3390/genes15111376
Vancouver
de Moraes RCM, Roth JR, Mao H, Crawley SR, Xu BP, Watson JC, et al. Apolipoprotein E Induces Lipid Accumulation Through Dgat2 That Is Prevented with Time-Restricted Feeding in Drosophila. Genes. 2024. doi:10.3390/genes15111376. PMID: 39596576.
BibTeX
@article{demoraes2024-39596576,
author = {de Moraes, Ruan Carlos Macêdo and Roth, Jonathan R. and Mao, Hailey and Crawley, Savannah R. and Xu, Brittney P. and Watson, John C. and Melkani, Girish C.},
title = {{Apolipoprotein E Induces Lipid Accumulation Through Dgat2 That Is Prevented with Time-Restricted Feeding in Drosophila}},
journal = {Genes},
year = {2024},
doi = {10.3390/genes15111376},
pmid = {39596576},
url = {https://doi.org/10.3390/genes15111376}
}
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