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Abstract

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, up 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 (MIDT).

Design
Measurements in four patients with the very rare disease of lipodystrophy (LD), resulting in leptin deficiency, and three untreated healthy control persons were performed at four different time points: before start and over twelve weeks of metreleptin treatment. Inside the MRI scanner, participants performed the MIDT and brain activity during the reward receipt phase of the trial was analyzed.

Results
We found increased brain activity in our four LD patients 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 three 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.