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Body mass regulation in humans is associated with dopamine synthesis capacity and dopamine receptor profile measured with positron emission tomography
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DOI：10.1038/s41398-026-04318-6.png)
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Abstract
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The widespread and increasing prevalence of excess body mass represents a major public health concern and has been hypothesized to involve dysfunction of the dopaminergic reward system. However, a detailed, systems-level understanding of interactions between the dopamine system and body mass regulation in humans has been elusive. To address this knowledge gap, we employed positron emission tomography (PET) to directly measure presynaptic dopamine synthesis capacity (with [18F]-FDOPA) and dopamine receptor availability (D1 and D2/3 receptors with [11C]-NNC112 and [18F]-Fallypride, respectively) in 117 individuals with body mass index (BMI) values ranging from normal to moderately obese. We found that elevated BMI was associated with heightened dopamine synthesis capacity in the midbrain and hypothalamus, key regions for homeostatic appetite control, as well as with lower D2/3 receptor availability in the midbrain, where D2 receptors play an important role in the autoregulation of striatal dopamine release. Moreover, we found that the presence and rate of weight gain in the 1–2 years prior to scanning was associated with increased presynaptic dopamine synthesis capacity in the ventral striatum and midbrain, important components of the reward network. These data suggest that upregulation of body mass beyond the normal range is related to increased dopamine synthesis capacity in reward- and homeostatic-related regions coupled with blunted autoregulation.
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