Evidence map›Paper›PMID 41917949›Full record

ArticleJournal of translational medicine2026

Macrophage FTO deficiency accelerates atherosclerosis via PACS2-mediated activation of the PPARγ lipid signaling pathway.

Jie Ouyang, Zishun Zhan, Haijiao Long, Shuhua Chen, Hong Xiang, Baiyi Tang, Quanjun Liu, Shiying Qin, Ye Tao, Alex F Chen and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Jie OuyangCenter for Experimental Medical Research, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Zishun ZhanDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Haijiao LongDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Shuhua ChenDepartment of Biochemistry, School of Life Sciences of Central South University, Changsha, Hunan, China.
Hong XiangCenter for Experimental Medical Research, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Baiyi TangIntensive Care Unit, Yueyang Central Hospital, Yueyang, Hunan, China.
Quanjun LiuDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Shiying QinDepartment of Biochemistry, School of Life Sciences of Central South University, Changsha, Hunan, China.
Ye TaoDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Alex F ChenCenter for Experimental Medical Research, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Hongwei LuCenter for Experimental Medical Research, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China. hongweilu@csu.edu.cn.ORCID 0000-0001-8005-142X

Funding

National Natural Science Foundation of China 82270519National Natural Science Foundation of China 82421001National Natural Science Foundation of China 82470475National Natural Science Foundation of China 82495172
6 · The paper itself

Abstract

backgroundAtherosclerosis, a leading cause of cardiovascular disease, is driven by abnormal lipid accumulation in arterial walls. However, the underlying molecular mechanisms remain incompletely understood. This study investigated the role of the macrophage-specific fat mass and obesity-associated gene (FTO) in atherogenesis.

methodsWe used an adeno-associated virus serotype 9 (AAV9) vector under the control of the F4/80 promoter to overexpress FTO in macrophages. The functional roles of FTO and its molecular interactions were investigated through Western blotting, RT-qPCR, coimmunoprecipitation, immunofluorescence, and MeRIP-qPCR assays.

resultsFTO expression was shown to be specifically reduced in macrophages. In primary peritoneal macrophages and RAW264.7 cells, reduced FTO expression increased lipid uptake and deposition. Overexpressing FTO significantly reduced high-fat diet (HFD)-induced atherosclerotic plaque formation and lipid accumulation in vivo. Mechanistically, FTO deficiency increased the mRNA stability of phosphofurin acidic cluster sorting protein 2 (PACS2) in an N6-methyladenosine (m6A)-dependent manner, thereby leading to elevated PACS2 protein levels and subsequent activation of the PPARγ pathway. This in turn resulted in increased expression of CD36 and PLIN2, which promoted lipid uptake and lipid droplet formation, respectively.

conclusionsOur findings identify a novel macrophage FTO-PACS2-PPARγ regulatory axis that plays a key role in lipid dysregulation and atherogenesis, thus highlighting FTO as a potential therapeutic target for atherosclerosis and related cardiovascular diseases.

Indexed as

Alpha-Ketoglutarate-Dependent Dioxygenase FTOAtherosclerosisLipid MetabolismMacrophagesPPAR gammaSignal TransductionAnimalsDiet, High-FatMaleMiceMice, Inbred C57BLPlaque, AtheroscleroticRAW 264.7 CellsAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, mousePPAR gammaAtherosclerosisFTOMacrophagePACS2PPARγ

Identifiers

PMID41917949
PMCPMC13154680

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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 OpenQuestion graph.