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

Abstract

Background: Obesity is a global health issue that contributes to the development of various diseases through metabolic dysregulation. Recent findings indicate that obesity leads to autophagy dysregulation, a cellular degradation process. Caloric restriction (CR) and CR combined with exercise (CR+Ex) are effective strategies for managing obesity and modulating autophagy. However, the regulation of autophagy and its signaling pathways 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 die 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. We examined body composition, skeletal muscle functions, and expression of autophagy signaling pathway in these mice. Result: Obesity resulted in increased body weight, lean mass, fat mass, and fat mass in tissue; decreased grip strength and endurance (P < 0.05). CR+Ex decreased body weight, lean mass, and fat mass in obese mice (P < 0.05). In red muscle, P62, LC3B-I and LC3B-II levels were elevated (P < 0.05), regardless of dietary conditions. High-fat diet induced Cathepsin L was reduced in red muscle (P < 0.05). Conclusion: Obesity leads to altered body composition and impaired skeletal muscle function, which are partially improved by CR+Ex. The modulation of the autophagy pathway was more pronounced in red muscle compared to white muscle, irrespective of the intervention. Autophagic activity was higher in red muscle compared to white muscle.