Selenoprotein P, a kind of hepatokine hormone secreted from the liver, has been found, through experiments with cultured muscle cells and mice and through clinical studies, to cause pathology named ‘exercise resistance,’ which prevents health promotion by physical exercise. The present results elucidate one of the reasons why individual responsiveness to exercise differs markedly as well as shed lights on development of therapy for lifestyle diseases due to lack of exercise, obesity and type-2 diabetes.