CONTEXT: Behaviorally, the most pronounced effects of leptin substitution in leptin deficiency are the hunger-decreasing and postprandial satiety-prolonging effects of the adipokine. Previously, with functional magnetic resonance imaging (MRI), we and others showed that eating behavior-controlling effects are at least in part conveyed by the reward system. However, to date, it is unclear if leptin only modulates eating behavior specific brain reward action or if it also alters the reward function of the brain unrelated to eating behavior. OBJECTIVE: We investigated with functional MRI the effects of metreleptin on the reward system in a reward task unrelated to eating behavior, the monetary incentive delay task. DESIGN: Measurements in 4 patients with the very rare disease of lipodystrophy (LD), resulting in leptin deficiency, and 3 untreated healthy control persons were performed at 4 different time points: before start and over 12 weeks of metreleptin treatment. Inside the MRI scanner, participants performed the monetary incentive delay task and brain activity during the reward receipt phase of the trial was analyzed. RESULTS: We found a reward-related brain activity decrease in our 4 patients with LD over the 12 weeks of metreleptin treatment in the subgenual region, a brain area associated with the reward network, which was not observed in our 3 untreated healthy control persons. CONCLUSIONS: These results suggest that leptin replacement in LD induces changes of brain activity during reward reception processing completely unrelated to eating behavior or food stimuli. This could suggest eating behavior-unrelated functions of leptin in the human reward system. TRIAL REGISTRATION: The trial is registered as trial No. 147/10-ek at the ethics committee of the University of Leipzig and at the State Directorate of Saxony (Landesdirektion Sachsen).

Day Clinic of Cognitive Neurology University of Leipzig 04103 Leipzig Germany

Department of Medicine University Hospital Leipzig 04103 Leipzig Germany

Department of Neurology Charles University 1st Faculty of Medicine and General University Hospital 12000 Prague Czech Republic

Helmholtz Institute for Metabolic Obesity and Vascular Research of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig 04103 Leipzig Germany

Institute of Nutritional Sciences Justus Liebig University 35390 Giessen Germany

Max Planck Institute for Human Cognitive and Brain Sciences 04103 Leipzig Germany

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