We did not measure or take account of physical activity or fitness, which is a limitation of our study, as the influence of exercise on leptin and adiponectin is well established: A meta-analysis of exercise interventions in children with obesity (40) and others in adults with pre-diabetes (41) and obesity (42) have described similar effects on adipokines as we have found here, but of lower magnitude. The gene discussed is ADIPOQ; the disease is obesity due to melanocortin 4 receptor deficiency.