Evidence map›Paper›PMID 41538457›Full record

ArticleScience (New York, N.Y.)2026

Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity.

Danhui Liu, Chuanli Zhou, Xiaochen Wang, Zhou Luo, Ruiyao Xu, Shanshan Huo, Lina Guo, Xuemei Luo, Shuhan Yang, Arielle Click and 10 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Trial
  2. Review
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  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Transcription start site heterogeneity controls MDA5 sensing of unspliced HIV-1 RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  10. CMPK2 restrictsbioRxiv : the preprint server for biology · 2026
    Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Danhui LiuDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-4074-0727
Chuanli ZhouDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1848-2055
Xiaochen WangDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-8911-3690
Zhou LuoDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-4884-0776
Ruiyao XuDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Shanshan HuoDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lina GuoDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Xuemei LuoDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0009-0000-1898-3365
Shuhan YangDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0009-0004-1715-0416
Arielle ClickDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-6777-1684
Janiece VancilDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Paola BarajasDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Victor MijaresDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hamid BaniasadiDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-1537-9354
Nan YanDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-0637-3989
Jan RehwinkelMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0003-3841-835X
Dustin C HancksDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-2720-2545
Elizabeth H ChenDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Shuang LiangDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-5250-1494
Zhenyu ZhongDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-9441-7645

Funding

UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeffrey M Zigman · 2022 to 2026
$7.4M
Decoding the mechanisms of cell-cell fusion - Renewal - 1R35GM136316 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI Elizabeth H Chen · 2020 to 2026
$3.1M
Deciphering the Role of dNTP Metabolism in Innate ImmunityR35GM142654 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI ZHONG, ZHENYU · 2021 to 2025
$2.2M
Evolution-guided Studies of Mitochondrial FunctionsR35GM142689 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI HANCKS, DUSTIN · 2021 to 2025
$2.0M
NIDDK NIH HHS P30 DK127984NIGMS NIH HHS R35 GM136316NIGMS NIH HHS R35 GM142654NIGMS NIH HHS R35 GM142689
6 · The paper itself

Abstract

Obesity is a major disease risk factor due to obesity-associated hyperinflammation. We found that obesity induced Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome hyperactivation and excessive interleukin (IL)-1β production in macrophages by disrupting SAM and HD domain-containing protein 1 (SAMHD1), a deoxynucleoside triphosphate (dNTP) hydrolase crucial for nucleotide balance. This caused aberrant accumulation of dNTPs, which can be transported into mitochondria, and initiated mitochondrial DNA (mtDNA) neosynthesis, which increased the presence of oxidized mtDNA and triggered NLRP3 hyperactivation. Deletion of SAMHD1 promoted NLRP3 hyperactivation in cells isolated from zebrafish, mice, and humans. SAMHD1-deficient mice showed elevated circulating IL-1β, insulin resistance, and metabolic dysfunction-associated steatohepatitis. Blocking dNTP mitochondrial transport prevented NLRP3 hyperactivation in macrophages from obese patients and SAMHD1-deficient mice. Our study revealed that obesity by inhibiting SAMHD1 rewired macrophage nucleotide metabolism, thereby triggering NLRP3 inflammasome hyperactivation to drive disease progression.

Indexed as

InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNucleotidesObesitySAM Domain and HD Domain-Containing Protein 1AnimalsDNA, MitochondrialFatty LiverHumansInsulin ResistanceInterleukin-1betaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutDNA, MitochondrialInflammasomesInterleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanNlrp3 protein, mouseNucleotidesSAM Domain and HD Domain-Containing Protein 1

Identifiers

PMID41538457
PMCPMC13034487

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.