Abstract
Studies in mice that are deficient in AMP-activated protein kinase (AMPK) have indicated that exercise-mediated reduction of fat mass requires activation of skeletal muscle AMPK. AMPK is a sensor of energy in cells and acts by increasing fat and glucose oxidation when energy production is required. Repeated exercise increases GLUT4, whereas a sedentary lifestyle decreases in GLUT4, in skeletal muscle. GLUT4 in the plasma membrane is responsible for glucose intake in skeletal muscle, and the increase in GLUT4 resulting from regular exercise is considered to be a major reason why regular exercise prevents diabetes mellitus. In serial studies of deleted GLUT4 minigene transgenic mice, exercise-responsive elements in the 5′-flanking sequence of the GLUT4 gene were located. Habitual fish consumption prevents myocardial infarction. Fish oil feeding activates PPARα, a transcription factor, that promotes β-oxidation of fatty acid, decreases the activity of SREBP-1c, a sterol regulatory element binding protein, and thus decreases lipogenesis. Both fish oil and fasting decrease SREBP-1c activity, but their mechanisms differ. Fibrate, an activator of PPARα, can prevent myocardial infarction, suggesting that the prevention of myocardial infarction by fish intake might be mediated by activation of PPARα. Regular exercise and fish intake affect the energy metabolism of the whole body, and help to prevent lifestyle-related disease. To develop new drugs and a strategy for prevention of lifestyle-related disease for individuals having different genetic backgrounds, it is necessary to understand how exercise and fish can prevent lifestyle-related disease.
