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

Obesity causes metabolic dysregulation and contributes to various diseases, with autophagy playing a pivotal role in this process. Autophagy, a cellular recycling mechanism, is influenced by factors beyond obesity, like caloric restriction (CR) and CR combined with exercise (CR+Ex), which modulate autophagy in obesity management. However, the regulation of autophagy in skeletal muscle under conditions of obesity, CR, and CR+Ex remains poorly understood.

Method

Mice were 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 four months, followed by the respective interventions for the subsequent four months. Body composition, motor function, and skeletal muscle autophagy signaling were assessed.

Results

Obesity resulted in increased total mass, lean mass, fat mass, and fat percentage in tissue; decreased grip strength and endurance capacity. Notably, CR+Ex reduced total mass, lean mass, and fat mass in obese mice. In both normal and obese conditions, the expression of autophagy markers p62, LC3B-I, and LC3B-II is significantly higher in red muscle. Obesity leads to a reduction in cathepsin L expression, while CR further increased LC3B-I expression in red muscle.

Conclusion

CR+Ex proves to be an effective strategy for counteracting the adverse changes in body composition associated with obesity. Unlike red muscle, white muscle exhibits lower baseline autophagic levels and may necessitate elevated expression of autophagy-related proteins, such as cathepsin L, to mitigate the negative effects of obesity.