Evidence map›Paper›PMID 40883493›Full record

ArticleScientific reports2025

Car4-positive adipocyte progenitor cells adapt to the aging environment and work as protection against ROS via glutathione metabolism.

Masato Horino, Kenji Ikeda, Rei Okazaki, Yujiro Nakano, Ryo Kaneda, Ryoko Ishii, Jun Aoki, Kazunari Hara, Akira Takeuchi, Yoshihiro Niitsu and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Masato HorinoDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Kenji IkedaDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan. kikeda.mem@tmd.ac.jp.
Rei OkazakiDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Yujiro NakanoDepartment of Endocrinology and Metabolism, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan.
Ryo KanedaDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Ryoko IshiiDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Jun AokiDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Kazunari HaraDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Akira TakeuchiDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Yoshihiro NiitsuDepartment of Diabetes and Endocrinology, Nissan Tamagawa Hospital, 4-8-1 Seta, Setagaya-ku, 158-0095, Tokyo, Japan.
Kuniyuki TaguchiDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Kuniyuki KanoDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
Masanori MurakamiDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Kazutaka TsujimotoDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Chikara KomiyaDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Tetsuya YamadaDepartment of Molecular Endocrinology and Metabolism, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan. tyammem@tmd.ac.jp.

Funding

AMED JP21gm6210011Japan Society for the Promotion of Science 21H02977JSPS 23K24385Moonshot Research and Development Program JPMJMS2023
6 · The paper itself

Abstract

The induction of beige adipocytes is significantly reduced in aged mice due to the senescence of adipocyte progenitor cells (APCs). Recent studies have revealed the existence of beige adipocyte subtypes, suggesting that APCs comprise a heterogeneous population. Therefore, in this study, we aimed to elucidate the mechanism through which long-term cold exposure induces the production of beige adipocytes even in aged mice. Single-cell RNA sequencing identified carbonic anhydrase 4 (Car4)-positive APCs. The number of Car4-positive APCs increased with age and cold exposure. Car4 knockdown (KD) mitigated intracellular pH reduction and significantly suppressed beige adipocyte differentiation. Furthermore, Car4 KD cells demonstrated reduced expression of genes in the glutathione pathway and increased susceptibility to reactive oxygen species (ROS), which was alleviated by glutathione supplementation. Our findings suggest that ROS resistance is an adaptation to the cellular aging environment. Our study provides insights into the age-related decline in beige adipocyte induction and identifies Car4 as a potential therapeutic target for enhancing energy expenditure in elderly individuals. This may pave the way for the development of new strategies to combat age-related metabolic diseases and offer hope for improved health and longevity in an aging population.

Indexed as

AdipocytesAdipocytes, BeigeAgingCarbonic AnhydrasesGlutathioneReactive Oxygen SpeciesStem CellsAdaptation, PhysiologicalAnimalsCell DifferentiationCellular SenescenceCold TemperatureMaleMiceMice, Inbred C57BLCarbonic AnhydrasesGlutathioneReactive Oxygen SpeciesAdipocyte progenitor cellsAgingBeige adipocytesCarbonic anhydrase 4GlutathioneReactive oxygen species

Identifiers

PMID40883493
PMCPMC12397281

What OpenQuestion 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 OpenQuestion graph.