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Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development
Wang X, He Q, Zhou C, Xu Y, Liu D, Fujiwara N, Kubota N, Click A et al.. Immunity, 2022-12-14
Topic: Brain proteins, microglia and lab models
Obesity-induced chronic liver inflammation is a hallmark of nonalcoholic steatohepatitis (NASH)-an aggressive form of nonalcoholic fatty liver disease. However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver. Here, we show that the macrophage phagocytic receptor TREM2, induced by hepatocyte-derived sphingosine-1-phosphate, was required for efferocytosis of lipid-laden apoptotic hepatocytes and thereby maintained liver immune homeostasis.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wang, X., He, Q., Zhou, C., Xu, Y., Liu, D., Fujiwara, N., et al. (2023). Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development. Immunity. https://doi.org/10.1016/j.immuni.2022.11.013
Vancouver
Wang X, He Q, Zhou C, Xu Y, Liu D, Fujiwara N, et al. Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development. Immunity. 2023. doi:10.1016/j.immuni.2022.11.013. PMID: 36521495.
BibTeX
@article{wang2023-36521495,
author = {Wang, X. and He, Q. and Zhou, C. and Xu, Y. and Liu, D. and Fujiwara, N. and Kubota, N. and Click, A. and others},
title = {{Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development}},
journal = {Immunity},
year = {2023},
doi = {10.1016/j.immuni.2022.11.013},
pmid = {36521495},
url = {https://doi.org/10.1016/j.immuni.2022.11.013}
}
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Key findings
- However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver.
- Here, we show that the macrophage phagocytic receptor TREM2, induced by hepatocyte-derived sphingosine-1-phosphate, was required for efferocytosis of lipid-laden apoptotic hepatocytes and thereby maintained liver immune homeostasis.
- However, prolonged hypernutrition led to the production of proinflammatory cytokines TNF and IL-1β in the liver to induce TREM2 shedding through ADAM17-dependent proteolytic cleavage.
- Loss of TREM2 resulted in aberrant accumulation of dying hepatocytes, thereby further augmenting proinflammatory cytokine production.
Why it matters
This study is about nonalcoholic steatohepatitis, showing that prolonged overnutrition caused TREM2 shedding and impaired clearance of dying liver cells, sustaining liver inflammation. It does not concern Alzheimer's disease and reports no treatment for it.
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Study details
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Immunity) |
| Journal's citation record | 4 / 4 | Immunity: journal h-index 567 (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 | 3 / 5 | 2023 — within 6 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 256 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 51.2 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 13.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 4 / 4 | Cited 228 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Zhenyu Zhong: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Duke University: institution h-index 1,541 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36521495) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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