In humans, with the exception of severe leptin deficiencies due to leptin mutations (congenital leptin deficiency, CLD) or lipodystrophies (generalized (GL) or partial lipodystrophies (PL))10–13, the majority of studies in overweight or obese populations with hyperleptinemia showed minimal if any effects of leptin treatment on weight or body composition14–22. Here, LEP is linked to congenital secretory chloride diarrhea 1.