Evidence mapPaperPMID 42356253Full record

ArticleNutrients2026

HMB and Liraglutide Confer Complementary Protection Against Lipotoxic and Atrophic Alterations in High-Glucose Plus Free Fatty Acid-Treated C2C12 Myotubes.

Li-Yuan Chen, Shao-Hsing Weng, Hsin-Hua Li, Chen-Hsing Su, Sing-Hua Tsou, Kuei-Chuan Chan, Chien-Ning Huang, Hui-Chih Hung, Sheng-Chieh Lin, Chih-Li Lin

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Article in Nutrients, 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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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Li-Yuan ChenInstitute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Shao-Hsing WengInstitute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.ORCID 0000-0002-9408-3542
Hsin-Hua LiDepartment of Exercise Health Science, National Taiwan University of Sport, Taichung 404, Taiwan.
Chen-Hsing SuDepartment of Neurosurgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Sing-Hua TsouDepartment of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan.ORCID 0000-0001-7574-028X
Kuei-Chuan ChanDepartment of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Chien-Ning HuangInstitute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Hui-Chih HungDepartment of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.ORCID 0000-0003-0180-1822
Sheng-Chieh LinSchool of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.ORCID 0000-0002-5771-6101
Chih-Li LinInstitute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.ORCID 0000-0003-4553-3727

Funding

Chung Shan Medical University Hospital CSH-2021-C-017National Chung Hsing University and Chung Shan Medical University NCHU-CSMU-11411National Science and Technology Council 114-2314-B-040-030-MY3National Science and Technology Council 114-2320-B-040-012-MY3National Science and Technology Council 114-2320-B-040-016
6 · The paper itself

Abstract

BACKGROUND/

objectivesType 2 diabetes (T2D)-associated sarcopenia is characterized by impaired insulin signaling, lipotoxicity, oxidative stress, and progressive muscle loss. Although liraglutide improves glucose control and reduces lipid burden, its ability to preserve muscle integrity under diabetic lipotoxic conditions remains limited. This study investigated whether β-hydroxy-β-methylbutyrate (HMB) could enhance liraglutide-mediated protection against high-glucose plus free fatty acid (HG+FFA)-induced injury in skeletal muscle cells.

methodsDifferentiated C2C12 myotubes were exposed to HG+FFA to establish a sublethal lipotoxic model and treated with liraglutide, HMB, or their combination. Cell viability, lipid accumulation, myotube morphology, insulin signaling, glucose uptake, mitochondrial function, reactive oxygen species (ROS), antioxidant gene expression, and atrophy-related signaling were assessed.

resultsHG+FFA induced marked lipid droplet accumulation, impaired insulin signaling, reduced glucose uptake, disrupted mitochondrial membrane potential, increased ROS production, suppressed antioxidant gene expression, and promoted an atrophic phenotype characterized by increased atrogin-1 and MuRF1 and reduced myogenic markers. Liraglutide alone reduced large lipid droplets and partially improved insulin signaling but showed limited efficacy in preserving the myotube phenotype. HMB alone exerted modest effects on lipid accumulation but preserved myotube area. Notably, combined HMB and liraglutide treatment more effectively reduced lipid burden, restored insulin signaling and glucose uptake, attenuated mitochondrial dysfunction and oxidative stress, restored antioxidant gene expression, and preserved MyHC-positive area and myotube diameter while suppressing atrogin-1/MuRF1 activation. These protective effects were largely attenuated by rapamycin, indicating at least partial dependence on mTOR-associated signaling.

conclusionsOverall, HMB and liraglutide exert complementary protective effects against diabetic lipotoxic and atrophic stress, supporting the potential utility of this combination strategy for T2D-associated sarcopenia.

Indexed as

Fatty Acids, NonesterifiedGlucoseLiraglutideMuscle Fibers, SkeletalMuscular AtrophyValeratesAnimalsCell LineCell SurvivalDiabetes Mellitus, Type 2InsulinMiceOxidative StressReactive Oxygen SpeciesSignal Transductionbeta-hydroxyisovaleric acidFatty Acids, NonesterifiedGlucoseInsulinLiraglutideReactive Oxygen SpeciesValeratesliraglutidemTOR signalingsarcopeniatype 2 diabetes (T2D)β-hydroxy-β-methylbutyrate (HMB)

Identifiers

PMID42356253
PMCPMC13304607

What Socratic holds

Texttitle and abstract
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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.