Evidence mapPaperPMID 40179260Full record

ArticleEndocrinology2025

Weight Gain With Advancing Age Is Controlled by the Muscarinic Acetylcholine Receptor M4 in Male Mice.

Toshio Takahashi, Yuta Takase, Akira Shiraishi, Shin Matsubara, Takehiro Watanabe, Shinji Kirimoto, Tohru Yamagaki, Masatake Osawa

Abstract read
In one paragraph

Article in Endocrinology, 2025. 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. 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

8 authors.

Toshio TakahashiSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan.ORCID 0000-0002-1822-0939
Yuta TakaseSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan.
Akira ShiraishiSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan.
Shin MatsubaraSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan.
Takehiro WatanabeSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan.
Shinji KirimotoAnimal Science Business Unit, KAC Co., Ltd., Kyoto 604-8423, Japan.
Tohru YamagakiSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan.
Masatake OsawaDepartment of Regenerative Medicine and Applied Biomedical Sciences, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan.

Funding

Grants-in-Aid for Scientific Research JP20K06751
6 · The paper itself

Abstract

Obesity is characterized by the excessive accumulation of adipose tissue, and it is a serious global health issue. Understanding the pathology of obesity is crucial for developing effective interventions. In this study, we investigated the role of muscarinic acetylcholine receptor M4 (mAChR-M4) in the regulation of obesity in Chrm4-knockout (M4-KO) mice. Male M4-KO mice showed higher weight gain and accumulation of white adipose tissue (WAT) with advancing age than the wild-type mice. The M4-KO mice also showed increased leptin expression at both the transcription and the translation levels. RNA sequencing and quantitative reverse transcription polymerase chain reaction analyses of subcutaneous adipose tissues revealed that the expression of WAT marker genes was significantly enhanced in the M4-KO mice. In contrast, the expression levels of brown adipose tissue/beige adipose tissue markers were strongly decreased in the M4-KO mice. To identify the Chrm4-expressing cell types, we generated Chrm4-mScarlet reporter mice and examined the localization of the mScarlet fluorescent signals in subcutaneous tissues. Fluorescent signals were prominently detected in WAT and mesenchymal stem cells. Additionally, we also found that choline acetyltransferase was expressed in macrophages, suggesting their involvement in acetylcholine (ACh) secretion. Corroborating this notion, we were able to quantitatively measure the ACh in subcutaneous tissues by liquid chromatography tandem mass spectrometry. Collectively, our findings suggest that endogenous ACh released from macrophages maintains the homeostasis of adipose cell growth and differentiation via mAChR-M4 in male mice. This study provides new insights into the molecular mechanisms underlying obesity and potential targets for therapeutic interventions.

Indexed as

AgingObesityReceptor, Muscarinic M4Weight GainAcetylcholineAdipose Tissue, BrownAdipose Tissue, WhiteAnimalsMaleMiceMice, Inbred C57BLMice, KnockoutAcetylcholineReceptor, Muscarinic M4acetylcholinebody weightbrown adipose tissuemuscarinic receptorwhite adipose tissue

Identifiers

PMID40179260
PMCPMC12012353

What Socratic holds

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LicenceCC BY
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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.