Intermittent fasting reduces mouse body fat while maintaining muscle mass by regulating protein synthesis and autophagy

The aim of this study is to investigate the effect of intermittent fasting (IF) on the regulation of skeletal muscle protein metabolism in response to nutrient supplementation during fasting.Twelve-week-old male C57BL/6J mice were assigned to two groups: ad libitum and IF, with the latter having access to food for only 3 h/d. After 6 wk of experimental periods, an oral glucose tolerance test was performed. One week later, phosphate-buffered saline or a glucose and branched-chain amino acid mixture was administered orally, and blood and tissues were collected 30 min later.The oral glucose tolerance test results revealed that the IF group had better insulin sensitivity. They also had lower body and fat weights while maintaining the same level of skeletal muscle mass as the ad libitum group. The phosphorylation of ribosomal protein S6 in the skeletal muscle, a marker for the activation of protein translation, was greater in the IF group after glucose and branched-chain amino acid mixture administration. Microtubule-associated protein light chain 3-II-to-light chain 3-I ratio, a marker for autophagosome formation, in skeletal muscle during fasting was significantly lower in the IF group than that in the ad libitum group.Our findings suggest that adaptation to IF regulates protein synthesis and breakdown, leading to the maintenance of skeletal muscle mass while reducing body fat.