Physical exercise influences cognitive function through a cascade of cellular processes that promote angiogenesis and neurogenesis. Autophagy is a cellular degradation system that is capable of producing energy in response to various conditions such as starvation, physical exercise and several treatments. Our previous report demonstrated that a disaccharide, trehalose, induced autophagy in the brain and reduced the levels of potentially toxic proteins. To achieve more efficient induction of autophagy in the brain, in this study, we examined the effect of disaccharide intake combined with exercise on autophagy in vivo. Consistent with the results of previous studies, our biochemical analyses demonstrated that trehalose increased the level of lipidated LC3 (LC3II) in the brain and liver of adult mice. However, contrary to our expectation, treadmill exercise reduced the level of LC3II in the brain and liver. Interestingly, glycogen storage was preserved in the liver of trehalose-intake mice even after exercise. Moreover, the trehalose transporter GLUT8 was increased in the liver by trehalose or in the brain by trehalose together with exercise. In contrast, the level of GLUT4 remained stable in the liver and brain even after exercise. These findings suggest that trehalose and GLUT8 coordinately contribute to energy supply in the brain. (C) 2019 Elsevier Inc. All rights reserved.