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Sarcopenia-related changes in serum GLP-1 level affect myogenic differentiation.

Hsien-Hao Huang1,2, Yun-Jie Wang3, Hui-Yu Jiang3

  • 1Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Journal of Cachexia, Sarcopenia and Muscle
|June 26, 2024
PubMed
Summary
This summary is machine-generated.

Elevated glucagon-like peptide 1 (GLP-1) levels in sarcopenia patients impair muscle differentiation by hindering glucose uptake and mitochondrial ATP production. This highlights a potential link between the gut and muscle health in sarcopenia.

Keywords:
ATP productionGLP‐1Glucose uptakeMicrotubule motor kinesin‐1Sarcopenia

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Area of Science:

  • Muscle physiology and aging
  • Gastrointestinal endocrinology
  • Metabolic homeostasis

Background:

  • Sarcopenia is characterized by progressive skeletal muscle decline.
  • Gastrointestinal conditions influence skeletal muscle metabolic homeostasis.
  • Gastrointestinal hormones may impact the myogenic program and sarcopenia development.

Purpose of the Study:

  • To investigate the association between gastrointestinal hormone levels and sarcopenia.
  • To identify specific gastrointestinal hormones linked to sarcopenia.
  • To elucidate the mechanisms by which these hormones affect myogenic differentiation.

Main Methods:

  • Categorized 145 individuals into sarcopenia and non-sarcopenia groups.
  • Measured plasma levels of gastrointestinal hormones.
  • Utilized immunofluorescence, western blotting, glucose uptake assays, seahorse analysis, flow cytometry, kinesin-1 assays, and qPCR to study myogenic differentiation.
  • Investigated the impact of glucagon-like peptide 1 (GLP-1) in a cell model.

Main Results:

  • Sarcopenia patients showed significantly higher plasma GLP-1 levels (1021.5 pg/mL) compared to non-sarcopenic individuals (351.1 pg/mL).
  • GLP-1 dose-dependently suppressed myogenic marker expression, myocyte fusion, and myotube formation.
  • GLP-1 inhibited kinesin-1 activity, impairing glucose transporter 4 (GLUT4) translocation and mitochondrial dispersion, reducing glucose uptake and ATP production.

Conclusions:

  • Elevated GLP-1 levels in sarcopenia are linked to reduced myogenic differentiation.
  • GLP-1 negatively impacts GLUT4 translocation and mitochondrial function, hindering energy production for muscle development.
  • Findings suggest targeting the muscle-gut axis for sarcopenia management and biomarker development.