Evidence mapPaperPMID 42522325Full record

ArticleJournal of cachexia, sarcopenia and muscle2026

Imeglimin Attenuates Skeletal Muscle Atrophy in Mouse Models of Obesity and Ageing.

Yangli Ye, Diandian Qian, Ikumi Nomura, Naoki Kobayashi, Yukiko Shimizu, Tadashi Okamura, Motoharu Awazawa, Kohjiro Ueki

Abstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 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

8 authors.

Yangli YeDepartment of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China.
Diandian QianDepartment of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China.
Ikumi NomuraDepartment of Molecular Diabetology, Diabetes Research Center, Japan Institute for Health Security, Tokyo, Japan.
Naoki KobayashiDepartment of Molecular Diabetology, Diabetes Research Center, Japan Institute for Health Security, Tokyo, Japan.
Yukiko ShimizuDepartment of Laboratory Animal Medicine, Japan Institute for Health Security, Tokyo, Japan.ORCID https://orcid.org/0000-0003-2120-3993
Tadashi OkamuraDepartment of Laboratory Animal Medicine, Japan Institute for Health Security, Tokyo, Japan.
Motoharu AwazawaDepartment of Molecular Diabetology, Diabetes Research Center, Japan Institute for Health Security, Tokyo, Japan.ORCID https://orcid.org/0009-0000-1576-4175
Kohjiro UekiDepartment of Molecular Diabetology, Diabetes Research Center, Japan Institute for Health Security, Tokyo, Japan.ORCID https://orcid.org/0000-0003-1523-8102

Funding

Sumitomo Pharma
6 · The paper itself

Abstract

backgroundSarcopenia is a major contributor to frailty and mortality in ageing and obesity and is tightly linked to metabolic dysfunction. Imeglimin is a first-in-class oral hypoglycaemic agent targeting mitochondrial function; however, despite the central role of mitochondria in skeletal muscle homeostasis, its effects on skeletal muscle under sarcopenia-relevant conditions remain unclear.

methodsImeglimin was administered to male C57BL/6 mice with high-fat diet (HFD)-induced obesity for 6 weeks and to naturally aged (18 months old) male mice for 12 weeks. Skeletal muscle fibre morphology and transcriptomic profiles were analysed in fast- and slow-twitch muscles. In parallel, C2C12 myotubes were exposed to palmitate with or without imeglimin, and inflammatory gene expression and reactive oxygen species (ROS) generation were assessed.

resultsImeglimin significantly increased the cross-sectional area (CSA) of Type II fibres in the extensor digitorum longus (EDL) muscle of HFD-fed mice (+66%, p < 0.01 vs. controls). Transcriptomic analyses revealed suppression of conserved molecular signatures of muscle atrophy, including activation of immediate-early genes and inflammatory pathways (-62% to -79%, p < 0.05 vs. HFD-fed mice). In palmitate-treated C2C12 myotubes, imeglimin attenuated lipotoxicity-induced inflammatory gene expression (-28% to -72%, p < 0.05 vs. controls) with reduced ROS generation, consistent with its cell-autonomous effect on myocytes. Notably, in naturally aged mice, 12-week imeglimin treatment preserved EDL muscle fibre size (+14%, p < 0.05 vs. controls) without altering systemic glucose tolerance, accompanied by transcriptomic changes overlapping with those observed in the HFD model (-27% to -82%, p < 0.05 vs. aged controls).

conclusionsImeglimin attenuates skeletal muscle atrophy in obesity and ageing, accompanied by coordinated suppression of stress- and inflammation-associated transcriptional programmes. These findings indicate that pharmacological regulation of mitochondrial stress responses influences skeletal muscle vulnerability under chronic metabolic stress and identify skeletal muscle as a previously underappreciated target of imeglimin action.

Indexed as

AgingMuscular AtrophyObesityAnimalsDiet, High-FatDisease Models, AnimalMaleMiceMice, Inbred C57BLMuscle, SkeletalReactive Oxygen SpeciesSarcopeniaReactive Oxygen Speciesageingimegliminmuscle atrophyobesitysarcopenia

Identifiers

PMID42522325
PMCPMC13416397

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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.