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Prolylcarboxypeptidase (PRCP) As a New Target for Obesity Treatment

Overview
Publisher Dove Medical Press
Specialty Endocrinology
Date 2010 Aug 10
PMID 20694162
Citations 5
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Abstract

Recently, we serendipitously discovered that mice with the deficiency of the enzyme prolylcarboxypeptidase (PRCP) have elevated alpha-melanocyte-stimulating hormone (alpha-MSH) levels which lead to decreased food intake and weight loss. This suggests that PRCP is an endogenous inactivator of alpha-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 alpha-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 alpha-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.

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References
1.
Manna S, Aggarwal B . Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J Immunol. 1998; 161(6):2873-80. View

2.
Boston B, Cone R . Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line. Endocrinology. 1996; 137(5):2043-50. DOI: 10.1210/endo.137.5.8612546. View

3.
Cone R, Mountjoy K, Robbins L, Nadeau J, Johnson K, Mortrud M . Cloning and functional characterization of a family of receptors for the melanotropic peptides. Ann N Y Acad Sci. 1993; 680:342-63. DOI: 10.1111/j.1749-6632.1993.tb19694.x. View

4.
Bagnol D, Lu X, Kaelin C, Day H, Ollmann M, Gantz I . Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. J Neurosci. 1999; 19(18):RC26. PMC: 6782481. View

5.
Jegou S, Boutelet I, Vaudry H . Melanocortin-3 receptor mRNA expression in pro-opiomelanocortin neurones of the rat arcuate nucleus. J Neuroendocrinol. 2000; 12(6):501-5. DOI: 10.1046/j.1365-2826.2000.00477.x. View