Regulation of fat metabolism by exercise-induced metabolic intermediates

초록

BACKGROUND Metabolic intermediates generated through exercise or dietary interventions play vital roles in body metabolism by serving as crucial molecules involved in various metabolic pathways. Among these intermediates, lactate and ketones hold significant importance and have specific functions in whole-body metabolism. Lactate, for instance, serves as a means to regenerate NAD+ for the continuation of glycolysis when oxygen is limited, by converting pyruvate to lactate. Beta-hydroxybutyrate (BHB), a major ketone body, is derived from the breakdown of fatty acids through a process of ketogenesis, which occurs when glucose supply is limited, such as during fasting. METHODS We investigated the roles of metabolic intermediates (lactate and BHB) in fat browning using in vitro and in vivo intervention models. Our intervention included a single-bout exercise under normal diet or fasting conditions, as well as 8-week endurance exercise training program with either a normal diet or a ketogenic diet. In the single-bout exercise intervention study, male SD rats underwent 24-hour fasting and/or a single-bout moderate intensity or high-intensity interval exercise (HIIE) in the fasted state. Additionally, young healthy male volunteers were randomly assigned into exercise intervention with intensity at onset of blood lactate accumulation (OBLA) or HIIE in the fasted state. In the 8-week endurance exercise training study, rats were subjected to aerobic exercise (40 min/day, 5 days/week) and/or ketogenic diet (KD). As an in vitro model, C2C12 myoblasts or differentiated myotubes were treated with metabolic intermediates. RESULTS Regardless of fasting, a single-bout exercise increased the concentration of lactate and BHB levels in rats, but exercise in the fasted state (F-EX) resulted in significantly higher BHB levels in both rats and humans. Interestingly, F-EX activated fat browning through the activation of AMPK/SIRT1/PGC1a pathway and PRDM16 upregulation, as well as th