Cited by 101Metabolism, Diabetes, and CancerMuscle Physiology and DisordersAdipose Tissue and Metabolism

GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway

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Wu, Luting, Zhou, Min, Li, Tianyou, Dong, Niu, Yi, Long, Zhang, Qianyong, Mi, Mantian·2022·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Abstract

Exercise-induced physical endurance enhancement and skeletal muscle remodeling can prevent and delay the development of multiple diseases, especially metabolic syndrome. Herein, the study explored the association between glucagon-like peptide-1 (GLP-1) secretion and exercise, and its effect on skeletal muscle remodeling to enhance endurance capacity. We found both acute exercise and short-term endurance training significantly increased the secretion of GLP-1 in mice. Recombinant adeno-associated virus (AAV) encoding Gcg (proglucagon) was used to induce the overexpression of GLP-1 in skeletal muscle of mice. Overexpression of GLP-1 in skeletal muscle enhanced endurance capacity. Meanwhile, glycogen synthesis, glucose uptake, type I fibers proportion, and mitochondrial biogenesis were augmented in GLP-1-AAV skeletal muscle. Furthermore, the in vitro experiment showed that exendin-4 (a GLP-1 receptor agonist) treatment remarkably promoted glucose uptake, type I fibers formation, and mitochondrial respiration. Mechanistically, the knockdown of AMPK could reverse the effects imposed by GLP-1R activation in vitro. Taken together, these results verify that GLP-1 regulates skeletal muscle remodeling to enhance exercise endurance possibly via GLP-1R signaling-mediated phosphorylation of AMPK.

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Crossref · 10.1016/j.bbamcr.2022.119300

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  • Interaction between GLP-1 and GLP-1R initiates AMPK signaling cascade within skeletal muscle tissue, leading to augmentation of mitochondrial biogenesis and improved oxidative metabolism.

    “The interaction between GLP-1 and its receptor GLP-1R initiates the AMPK signaling cascade within skeletal muscle tissue. This initiation precipitates a multitude of alterations in the cellular milieu, notably the augmentation of mitochondrial biogenesis-a mechanism responsible for the genesis of new mitochondria. Furthermore, GLP-1 augments mitochondrial efficacy, as manifested by the ameliorated”

    From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [389]

    Sections 3.4 and 3.5 (page numbers unavailable) report increased markers of mitochondrial biogenesis and respiration after GLP-1 or GLP-1R agonist treatment, and show that AMPK knockdown blocked the oxidative-metabolism effect. The Discussion describes GLP-1R-mediated AMPK phosphorylation as a probable mechanism, so the claim overstates that proposed pathway as an established sequence. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Overexpression of GLP-1 in skeletal muscle can improve endurance.

    “Overexpression of GLP-1 in skeletal muscle can improve endurance.”
  • Mitochondrial content and function in skeletal muscle are regulated by GLP-1.

    “Mitochondrial content and function in skeletal muscle are regulated by GLP-1.389”
  • These cellular transformations contribute significantly to enhanced endurance during exercise, underscoring critical role of GLP-1 in regulation of mitochondrial function and content in skeletal muscle.

    “These cellular transformations contribute significantly to enhanced endurance during exercise, thereby underscoring the critical role that GLP-1 plays in the regulation of mitochondrial function and content in skeletal muscle.389”
  • GLP-1 enhances physical endurance by inducing skeletal muscle remodeling, which may be mediated by GLP-1R/AMPK signaling.

    “We demonstrated that GLP-1 enhances physical endurance by inducing skeletal muscle remodeling, which may be mediated by GLP-1R/AMPK signaling.389”

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Authors
Wu, L., Zhou, M., Li, T., Dong, N., Yi, L., Zhang, Q., & Mi, M.
Affiliations
Army Medical University (CN)
Corresponding author
  • Zhang, Qianyong
  • Mi, Mantian
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Publisher
Elsevier BV
Published
2022-09
Volume
1869
Issue
9
Pages
119300
ISSN
0167-4889 (ISSN-L)
OpenAlex
W4281979657
Cited by
101
References
39
Citations by year
2026: 23 · 2025: 40 · 2024: 29 · 2023: 7 · 2022: 2
FWCI
6.37
Type
journal article
Language
en
Open access
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81773408, AWS17J014, 81903310)
  • Natural Science Foundation of Chongqing (cstc2019jcyj, 81773408, 81903310, AWS17J014, cstc2019jcyj-msxmX0201)
  • Army Medical University (AWS17J014)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
glucagon-like peptide-1, exercise endurance, skeletal muscle remodeling, GLP-1 receptor, AMPK signaling, exendin-4, type I muscle fibers, mitochondrial biogenesis, glucose uptake, glycogen synthesis, metabolic syndrome
MeSH terms
Glucagon-Like Peptide-1 Receptor, Animals, Glucose, Mice, Inbred C57BL, Physical Conditioning, Animal, Muscle, Skeletal, Mice, Glucagon-Like Peptide 1, AMP-Activated Protein Kinases

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