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We investigated whether calorie restriction (CR) enhances metabolic adaptations to endurance training (ET). Ten-week-old male Institute of Cancer Research (ICR) mice were fed ad libitum or subjected to 30% CR. The mice were subdivided into sedentary and ET groups. The ET group performed treadmill running (20-25 m/min, 30 min, 5 days/week) for 5 weeks. We found that CR decreased glycolytic enzyme activity and monocarboxylate transporter (MCT) 4 protein content, while enhancing glucose transporter 4 protein content in the plantaris and soleus muscles. Although ET and CR individually increased citrate synthase activity in the plantaris muscle, the ET-induced increase in respiratory chain complex I protein content was counteracted by CR. In the soleus muscle, mitochondrial enzyme activity and protein levels were increased by ET, but decreased by CR. It has been suggested that CR partially interferes with skeletal muscle adaptation to ET. Keywords: Endurance training, Calorie restriction, Mitochondria, Enzyme, Transporter, Gluconeogenesis, Skeletal muscle, Liver, Author(s): Kenya Takahashi[sup.1], Yu Kitaoka[sup.2] and Hideo Hatta[sup.1] Background Weight loss is beneficial for preventing metabolic disorders in overweight and obese individuals [1, 2] and improving the power-to-body weight ratio [...]