Evidence map›Paper›PMID 40770269›Full record

ArticleScientific reports2025

Mild hypothermia attenuates hepatic ischemia-reperfusion injury by regulating FoxO1/PPARα pathway.

Zhongshan Lu, Hao Chen, Anxiong Liu, Shufang Na, Wei Wang, Zibiao Zhong, Qifa Ye

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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

7 authors.

Zhongshan Lu *Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Provincial Clinical Research Center for Natural Polymer Biological Liver, Wuhan, 430071, Hubei, China.
Hao Chen *Organ Transplant Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan Province, China.
Anxiong LiuZhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Provincial Clinical Research Center for Natural Polymer Biological Liver, Wuhan, 430071, Hubei, China.
Shufang NaZhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Provincial Clinical Research Center for Natural Polymer Biological Liver, Wuhan, 430071, Hubei, China.
Wei WangDepartment of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. doctorwangwei@whu.edu.cn.
Zibiao ZhongZhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Provincial Clinical Research Center for Natural Polymer Biological Liver, Wuhan, 430071, Hubei, China. hizzb@whu.edu.cn.
Qifa YeZhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Provincial Clinical Research Center for Natural Polymer Biological Liver, Wuhan, 430071, Hubei, China. yqf_china@163.com.

Funding

National Natural Science Foundation of China 81970548
6 · The paper itself

Abstract

Hepatic ischemia-reperfusion injury (IRI) is a common complication of hepatectomy and liver transplantation. As far as we know, mild hypothermia (MH) is an effective measure to alleviate liver IRI. However, the precise mechanisms have not been fully elucidated. This study investigated the regulatory role of FoxO1/PPARα-mediated energy metabolism in MH-alleviated IRI. Results showed a significant reduction in PPARα expression during liver IRI. Moreover, high PPARα level in post-IR liver specimens correlated with improved liver transplantation outcomes. MH increased blood glucose, elevated gluconeogenesis, and promoted fatty acid oxidation (FAO), indicating a high metabolic state, and also enhanced PPARα expression. Additionally, PPARα promoted FAO and gluconeogenesis, thereby enhancing MH's protective effects on hepatocytes. Mechanistically, MH promoted FoxO1-PPARα interaction, enhancing PCK1 and CPT1a transcription and boosting hepatic metabolism. Selective FoxO1 inhibition by AS1842856 worsened IRI and apoptosis by reducing gluconeogenesis and FAO, MH partially mitigated this damage and promoted energy metabolism. Additionally, through the FoxO1/PPARα pathway, MH inhibits BAX/Cytochrome C/Caspase-3 cascade-initiated apoptosis. Our findings suggest that MH alleviates liver IRI by activating FoxO1/PPARα-mediated energy metabolism and inhibiting the mitochondria-dependent apoptosis pathway, potentially providing a basis for broader MH application.

Indexed as

Forkhead Box Protein O1Hypothermia, InducedLiverPPAR alphaReperfusion InjuryAnimalsApoptosisEnergy MetabolismFatty AcidsGluconeogenesisHepatocytesHumansLiver TransplantationMaleMiceMice, Inbred C57BLFatty AcidsForkhead Box Protein O1Foxo1 protein, mousePPAR alphaFatty acid oxidationFoxO1GluconeogenesisIschemia-reperfusion injuryMild hypothermiaPPARα

Identifiers

PMID40770269
PMCPMC12328581

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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.