Evidence map›Paper›PMID 41507908›Full record

ArticleLipids in health and disease2026

Alternative polyadenylation mediated the downregulation of lysophosphatidylglycerol acyltransferase 1 in metabolic dysfunction-associated steatotic liver disease.

Wei Feng, Yuxin Liu, Yunxiao Zhang, Aowen Tian, Miaoran Zhang, Peng Xu, Chang Shu, Jianping Wen, Jianli Yang, Baiyu Qi and 3 more

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In one paragraph

Article in Lipids in health and disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Wei FengDepartment of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin Province, 130021, China.
Yuxin LiuDepartment of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin Province, 130021, China.
Yunxiao ZhangDepartment of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin Province, 130021, China.
Aowen TianDepartment of Geriatrics, Tianjin Key Laboratory of Elderly Health, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin 300052, 300041, China.
Miaoran ZhangDepartment of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin Province, 130021, China.
Peng XuDepartment of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Jilin University, Changchun, Jilin Province, 130021, China.
Chang ShuDepartment of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Jilin University, Changchun, Jilin Province, 130021, China.
Jianping WenDepartment of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin Province, 130021, China.
Jianli YangDepartment of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin Province, 130021, China.
Baiyu QiDepartment of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin Province, 130021, China.
Wenjin QiuDepartment of Neurobiology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, 550000, China.
Zhengwen AnDepartment of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China.
Peng ChenDepartment of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin Province, 130021, China. pchen@jlu.edu.cn.

Funding

the National Key R&D Program of China No. 2022YFC2504200the National Natural Science Foundation of China No. 82270960the Natural Science Foundation of Jilin Province 20240101272JCthe Science & Technology Development Talent Project of Jilin Financial Department, Jilin, China No. JCSZ2021893-35
6 · The paper itself

Abstract

backgroundAlternative polyadenylation (APA) is a critical post-transcriptional regulatory mechanism involved in various diseases. Studies have shown dysfunction of APA-regulating factors such as SRSF10 in metabolic dysfunction-associated steatotic liver disease (MASLD). However, the downstream target genes and functional consequences remain unclear. This study investigated the role of APA in modulating LPGAT1 expression in MASLD.

methodsIntegrative analyses of bulk and single-cell RNA sequencing data from human and mouse MASLD livers were performed to identify APA changes. Functional validations were conducted using lysophosphatidylglycerol acyltransferase 1 (LPGAT1) 3’ UTR (3’ untranslated region)-knockout HepG2 cells under free fatty acid (FFA) treatment.

resultsEarly hepatocyte-specific APA remodeling characterized by 3’ lengthening of metabolism-related genes, especially LPGAT1, was observed in MASLD. Despite elevated LPGAT1 mRNA levels, protein levels were suppressed in MASLD, associated with an increased usage of a proximal 3’ UTR segment enriched with miRNA binding sites. Deletion of this proximal region in HepG2 cells restored LPGAT1 protein levels and mitigated lipid accumulation under FFA exposure.

conclusionsThis study establishes a cell type-resolved APA regulatory map for the MASLD liver and identifies APA-mediated repression of LPGAT1 as a critical driver of hepatic lipid accumulation. These findings highlight APA regulation as not only a pathogenic mechanism but also a promising molecular target for therapeutic interventions aimed at combating the progression of metabolic liver disease.

Indexed as

1-Acylglycerophosphocholine O-AcyltransferaseFatty LiverPolyadenylation3' Untranslated RegionsAnimalsDown-RegulationHep G2 CellsHumansLiverMiceMicroRNAsRNA, Messenger1-Acylglycerophosphocholine O-Acyltransferase3' Untranslated RegionsLpcat1 protein, humanMicroRNAsRNA, Messenger3' Untranslated regionsAlternative polyadenylationHepatocytesLysophosphatidylglycerol acyltransferase 1Metabolic dysfunction-associated steatotic liver diseasemiR-219-5p

Identifiers

PMID41507908
PMCPMC12879358

What Socratic holds

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LicenceCC BY-NC-ND
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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.