Evidence map›Paper›PMID 38834654›Full record

ArticleNature communications2024

FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC.

Rong Li, Xijing Yan, Cuicui Xiao, Tingting Wang, Xuejiao Li, Zhongying Hu, Jinliang Liang, Jiebin Zhang, Jianye Cai, Xin Sui and 12 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing 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

57 citing papers in PubMed.

  1. Review
  2. ACSL4-Dependent Lysosomal Lipid Peroxidation Links WTAP-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

22 authors.

Rong Li *Guangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.ORCID http://orcid.org/0000-0003-4951-577X
Xijing Yan *Guangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Cuicui Xiao *Department of Anesthesiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Tingting Wang *Guangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Xuejiao Li *Guangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.ORCID http://orcid.org/0000-0003-4197-4509
Zhongying HuGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Jinliang LiangGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.ORCID http://orcid.org/0000-0002-9386-0645
Jiebin ZhangGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Jianye CaiGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Xin SuiSurgical ICU, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Qiuli LiuThe Biotherapy Center, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
Manli WuDepartment of ultrasound, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
Jiaqi XiaoGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.ORCID http://orcid.org/0000-0002-3253-9591
Haitian ChenGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.ORCID http://orcid.org/0000-0002-3292-5521
Yasong LiuGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.ORCID http://orcid.org/0000-0002-9919-2051
Chenhao JiangGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Guo LvGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Guihua ChenGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Yingcai ZhangGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. zhangyc3@mail.sysu.edu.cn.
Jia YaoGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. yaojia6@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0003-1457-7241
Jun ZhengGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. zhengj67@mail2.sysu.edu.cn.ORCID http://orcid.org/0000-0002-4283-0403
Yang YangGuangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. yysysu@163.com.

Funding

China Postdoctoral Science Foundation 2022M713617China Postdoctoral Science Foundation 2022M713621National Natural Science Foundation of China (National Science Foundation of China) 81802897, 81901943, 81972286, 81970567National Natural Science Foundation of China (National Science Foundation of China) 81900597National Natural Science Foundation of China (National Science Foundation of China) 81970567National Natural Science Foundation of China (National Science Foundation of China) 82170631National Natural Science Foundation of China (National Science Foundation of China) 82202191
6 · The paper itself

Abstract

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation.

Indexed as

Alpha-Ketoglutarate-Dependent Dioxygenase FTOCoenzyme A LigasesFerroptosisLiverReceptors, TransferrinReperfusion InjuryUp-RegulationAnimalsAntigens, CDHumansLiver TransplantationMaleMiceMice, Inbred C57BLRNA StabilityAcsl4 protein, mouseAlpha-Ketoglutarate-Dependent Dioxygenase FTOAntigens, CDCD71 antigenCoenzyme A LigasesFTO protein, mouseReceptors, Transferrin

Identifiers

PMID38834654
PMCPMC11150474

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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 OpenQuestion graph.