Krawczewski and co-authors found that voluntary exercise in a mouse strain susceptible to diet-induced obesity decreased fat mass & increased energy expenditure via activation of leptin receptor-positive neurons in the ventromedial nucleus; in this study, intracerebral leptin did not decrease body weight or food intake in sedentary mice fed high fat diets but did reduce body weight in exercising mice. The gene discussed is LEPR; the disease is obesity due to melanocortin 4 receptor deficiency.