Muscle Type-Specific Modulation of Autophagy Signaling in Obesity: Effects of Caloric Restriction and Exercise

Background : Obesity causes metabolic dysregulation and contributes to diseases, and autophagy plays a pivotal role in that process. In mice, autophagy, a cellular recycling mechanism, is influenced by factors beyond obesity, including caloric restriction (CR) and CR combined with voluntary wheel ru...

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Bibliographic Details
Main Authors: Fujue Ji, Jong-Hee Kim
Format: Article
Language:English
Published: Korean Society for the Study of Obesity 2025-07-01
Series:Journal of Obesity & Metabolic Syndrome
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Online Access:http://www.jomes.org/journal/view.html?doi=10.7570/jomes24048
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Summary:Background : Obesity causes metabolic dysregulation and contributes to diseases, and autophagy plays a pivotal role in that process. In mice, autophagy, a cellular recycling mechanism, is influenced by factors beyond obesity, including caloric restriction (CR) and CR combined with voluntary wheel running (CR+Ex). However, the regulation of autophagy in skeletal muscle during obesity, CR, and CR+Ex remains poorly understood. Methods : Mice (n=42) were randomly divided into six groups: normal diet, normal diet CR, normal diet CR+Ex, high-fat diet, high-fat diet CR, and high-fat diet CR+Ex. All mice were fed ad libitum with either a normal or high-fat diet for the first 4 months, followed by the respective interventions for the subsequent 4 months. Body composition, motor function, and autophagy signaling were assessed. Results : Obesity resulted in increased total mass, lean mass, fat mass, and fat percentage in tissue and decreased grip strength and endurance capacity. Notably, CR+Ex reduced total mass, lean mass, and fat mass in obese mice. In both the normal and obese conditions, the expression of the autophagy markers p62, light chain 3B (LC3B)-I, and LC3B-II was significantly higher in red muscle than white muscle. Obesity led to a reduction in cathepsin L expression, and CR further increased LC3B-I expression in red muscle. Conclusion : CR+Ex was an effective strategy for counteracting the adverse changes in body composition associated with obesity. Compared with red muscle, white muscle exhibits lower autophagy-related protein levels and might require elevated cathepsin L expression to mitigate the negative effects of obesity.
ISSN:2508-6235