Evidence map›Paper›PMID 41316307›Full record

ArticleCell & bioscience2025

RNF186 controls glucose metabolism in metabolic dysfunction-associated fatty liver disease.

Jiang Du, Qizhang Du, Yuxuan Zhang, Jingwen Gao, Chiheng Wang, Beilin Kou, Yan Jiang, Dunyong Zhao, Juntang Lin

Erratum issuedAbstract read
In one paragraph

Article in Cell & bioscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Jiang Du *Henan Collaborative Innovation Center of Stem Cells and Biotherapy, School of Medical Engineering, Henan Medical University (Xinxiang Medical University), East of Jinsui Road #601, Xinxiang, 453003, Henan Province, China.
Qizhang Du *Henan Collaborative Innovation Center of Stem Cells and Biotherapy, School of Medical Engineering, Henan Medical University (Xinxiang Medical University), East of Jinsui Road #601, Xinxiang, 453003, Henan Province, China.
Yuxuan ZhangHenan Collaborative Innovation Center of Stem Cells and Biotherapy, School of Medical Engineering, Henan Medical University (Xinxiang Medical University), East of Jinsui Road #601, Xinxiang, 453003, Henan Province, China.
Jingwen GaoHenan Collaborative Innovation Center of Stem Cells and Biotherapy, School of Medical Engineering, Henan Medical University (Xinxiang Medical University), East of Jinsui Road #601, Xinxiang, 453003, Henan Province, China.
Chiheng WangHenan Collaborative Innovation Center of Stem Cells and Biotherapy, School of Medical Engineering, Henan Medical University (Xinxiang Medical University), East of Jinsui Road #601, Xinxiang, 453003, Henan Province, China.
Beilin KouFirst College for Clinical Medicine, Henan Medical University (Xinxiang Medical University), Xinxiang, 453003, Henan, China.
Yan JiangSchool of Nursing, Henan Medical University (Xinxiang Medical University), Xinxiang, 453003, China.
Dunyong ZhaoDepartment of Gastroenterology, Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, 400038, China. zdy930@163.com.
Juntang LinHenan Collaborative Innovation Center of Stem Cells and Biotherapy, School of Medical Engineering, Henan Medical University (Xinxiang Medical University), East of Jinsui Road #601, Xinxiang, 453003, Henan Province, China. linjtlin@126.com.

Funding

Natural Science Foundation of China U1804186Natural Science Foundation of Henan Province 235101610002Natural Science Foundation of Henan Province 242300421199Natural Science Foundation of Henan Province 252300420147
6 · The paper itself

Abstract

BACKGROUND AND

aimsRNF186, which encodes a ring-finger domain-containing E3 ubiquitin-protein ligase, has previously been implicated in the regulation of lipid metabolic disorders associated with metabolic dysfunction-related fatty liver disease (MAFLD). However, the precise mechanism by which RNF186 influences glucose metabolism in the context of MAFLD remains unclear. In this study, we aimed to elucidate the role of RNF186 in the regulation of glucose metabolism, with a particular focus on skeletal muscle.

methodsIn vitro, we treated skeletal myocytes and hepatocytes with high glucose concentrations to study the expression of RNF186 and its effects on glucose uptake and insulin signaling. In vivo, we developed a MAFLD model through long-term high-fat feeding and assessed the impact of RNF186 deficiency on glucose metabolism in skeletal muscle, liver and adipose tissue using Western blotting, quantitative PCR (qPCR), and immunofluorescence.

resultsOur findings demonstrate that RNF186 is regulated by glucose concentration in skeletal muscle cells and hepatocytes and is sensitive to insulin in a high-glucose environment. The deletion of RNF186 increases glucose metabolism and alleviates insulin signaling disruption in the MAFLD model, affecting skeletal muscle, liver, and adipose tissue. Furthermore, in skeletal muscle, RNF186 deficiency reduces the ER stress-mediated unfolded protein response (UPR) by preventing the ubiquitination of ATF6, leading to increased transcription of GLUT4. Additionally, RNF186 deficiency promotes the membrane translocation of GLUT4 via the AKT/TBC1D4 signaling pathway. In contrast, overexpression of RNF186 decreases AKT signaling and GLUT4 expression, resulting in exacerbated disruption of glucose metabolism in MAFLD.

conclusionsRNF186 regulates glucose metabolism across multiple tissues in MAFLD, notably by playing a dual role in modulating the transcription and translocation of GLUT4 in skeletal muscle. These findings suggest that targeting the expression of RNF186 could be a potential therapeutic strategy for treating MAFLD and related metabolic disorders.

Indexed as

Glucose metabolismGLUT4Metabolic dysfunction-associated fatty liver diseaseRNF186Skeletal muscle

Identifiers

PMID41316307
PMCPMC12661674

What Socratic holds

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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.