J Obes Metab Syndr.  2025 Jul;34(3):303-314. 10.7570/jomes24048.

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

• Ji F
• Kim JH

• KMID: 2570639
• DOI: http://doi.org/10.7570/jomes24048

Abstract

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 highfat 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.

Keyword

Obesity; Skeletal muscle; Autophagy; Caloric restriction; Voluntary wheel running