Evidence mapPaperPMID 40930346Full record

ArticleJournal of advanced research2026

Loss of hepatic ME1 ameliorates MASLD by Suppressing peroxisomal β-Oxidation and Activating Lipophagy/Lipolysis.

Jiawei Zhang, Danyi Wu, Ruoxuan Lei, Feifei Zhang, Wei Wu, Yu Wu, Zhihao Zhang, Dan Han, Luyi Chen, Yingying Yu and 3 more

Abstract read
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
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  3. 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

13 authors.

Jiawei ZhangSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China; Xinjie Branch of Traditional Chinese Medicine Hospital of Xiaoshan District, Xiaoshan, Hangzhou, China.
Danyi WuSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China.
Ruoxuan LeiSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China.
Feifei ZhangSchool of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China.
Wei WuSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China.
Yu WuSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China.
Zhihao ZhangSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China.
Dan HanDepartment of Nutrition and Food Safety, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
Luyi ChenDepartment of General Practice, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yingying YuSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China.
Li JiangSchool of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China.
Jun YangSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China.
Xuexian FangSchool of Public Health and Nursing, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Hangzhou, China. Electronic address: xfang@hznu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionMetabolic dysfunction-associated steatotic liver disease (MASLD) represents an increasing global health problem in association with obesity and insulin resistance without approved pharmacotherapy. Previous studies revealed malic enzyme 1 (ME1) as a susceptibility gene for metabolic disorders in humans. However, the role and mechanisms of ME1 in regulating hepatic lipid metabolism remain largely unclear.

objectivesThis study aimed to investigate the roles, mechanisms, and therapeutic potential of ME1 in regulating MASLD.

methodsHepatic expression of ME1 gene and protein were characterized in MASLD patients and three MASLD mouse models. Using a hepatocyte-specific Me1 knockout model, we assessed the effects of the gene on diet-induced or age-dependent MASLD. Oleic and palmitic acids were used to mimic hepatic lipid accumulation in vitro. Molecular mechanisms underlying ME1 function were investigated through RNA sequencing, biochemical analyses, and pharmacological intervention.

resultsME1 demonstrates a positive correlation with MASLD progression in both mouse models and human patients. Hepatocyte-specific deletion of Me1 gene reduced body weight, attenuated insulin resistance, and improved hepatic steatosis after 16 weeks of high-fat diet (HFD) feeding. Besides, the detrimental effects of Me1 on fatty liver and associated pathologies are observed in aged knockout mice. Conversely, overexpressing ME1 exacerbated MASLD in vitro and in vivo. Transcriptome analyses uncovered that in response to HFD, acyl-CoA oxidase 1 (Acox1)-mediated peroxisomal fatty acid β-oxidation was remarkably suppressed in Me1-deficient livers, thereby disrupting the downstream production of acetyl-CoA and H

conclusionsOur study provides the first demonstration that ME1 regulates ACOX1-mediated peroxisomal β-oxidation and subsequent lipophagy/lipolysis, revealing its pivotal lipid-regulatory role in MASLD. These findings underscore ME1 as a promising target for treating MASLD and associated liver pathologies.

Indexed as

AutophagyFatty LiverLipolysisLiverMalate DehydrogenasePeroxisomesAnimalsDiet, High-FatDisease Models, AnimalHepatocytesHumansInsulin ResistanceLipid MetabolismMaleMiceMice, Inbred C57BLMalate DehydrogenaseLipolysisLipophagyMalic enzyme 1MASLDPeroxisome

Identifiers

PMID40930346
PMCPMC13227285

What Socratic holds

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Registered trials

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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 Socratic graph.