Prolylcarboxypeptidase (PRCP) as a new target for obesity treatment

B Shariat-Madar¹, D Kolte², A Verlangieri², Z Shariat-Madar²

¹College of Literature, Science, and the Arts, University of Michigan, Ann Arbor MI, USA; ²School of Pharmacy, Department of Pharmacology, University of Mississippi, University, MS, USA

Abstract: Recently, we serendipitously discovered that mice with the deficiency of the enzyme prolylcarboxypeptidase (PRCP) have elevated α-melanocyte-stimulating hormone (α-MSH) levels which lead to decreased food intake and weight loss. This suggests that PRCP is an endogenous inactivator of α-MSH and an appetite stimulant. Since a modest weight loss can have the most profound influence on reducing cardiovascular risk factors, the inhibitors of PRCP would be emerging as a possible alternative for pharmacotherapy in high-risk patients with obesity and obesity-related disorders. The discovery of a new biological activity of PRCP in the PRCP-deficient mice and studies of α-MSH function indicate the importance and complexity of the hypothalamic pro-opiomelanocortin (POMC) system in altering food intake. Identifying a role for PRCP in regulating α-MSH in the brain may be a critical step in enhancing our understanding of how the brain controls food intake and body weight. In light of recent findings, the potential role of PRCP in regulating fuel homeostasis is critically evaluated. Further studies of the role of PRCP in obesity are much needed.

Keywords: prolylcarboxypeptidase, melanocyte-stimulating harmone, appetite, weight loss, cardiovascular risk, obesity