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

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.