Reduced levels of neurotransmitter-degrading enzyme PRCP promote a lean phenotype. [corrected].

The level of neurotransmitters present in the synaptic cleft is a function of the delicate balance among neurotransmitter synthesis, recycling, and degradation. While much is known about the processes controlling neurotransmitter synthesis and release, the enzymes that degrade peptide neurotransmitters are poorly understood. A new study in this issue of the JCI reveals the important role of neuropeptide degradation in regulating obesity (see the related article beginning on page 2291). Wallingford et al. provide evidence that, in mice, the enzyme prolylcarboxypeptidase (PRCP) degrades alpha-melanocyte-stimulating hormone (alpha-MSH) to an inactive form that is unable to inhibit food intake. Their studies indicate that PRCP expression promotes obesity, while inhibitors of the enzyme counteract obesity.