Circulating serotonin levels in the periphery are dependent on the expression of Tph1 within the gastrointestinal tract (for review see refs. 15,16), yet surprisingly, the genetic deletion of Tph1 within the gastrointestinal tract does not result in a lean phenotype17, which is in contrast to the anti-obesity phenotype of germline deletion13,14. The gene discussed is TPH1; the disease is obesity due to melanocortin 4 receptor deficiency.