The peptide alpha-MSH works in a region of the brain known as the hypothalamus to suppress appetite. A team of researchers, at Yale University School of Medicine, New Haven, and the University of California Davis, has provided new insight into the way in which levels of the active form of alpha-MSH are regulated in mice. Specifically, genetic and biochemical analysis performed by the team, led by Sabrina Diano and Craig Warden, indicated that the protein PRCP is expressed in the hypothalamus and breaks down the active form of alpha-MSH, generating a slightly smaller peptide that does not suppress food intake. Importantly, administration of PRCP inhibitors to both normal and obese mice reduced their food intake. Further, mice lacking PRCP had increased levels of the active form of alpha-MSH in the hypothalamus and were leaner and shorter than normal mice; they also did not get obese when fed a high-fat diet. The authors suggest that these data are the first step in identifying PRCP as a candidate drug target for the treatment of obesity and obesity-related disorders. Although Richard Palmiter, at the University of Washington, Seattle, also raises this intriguing possibility, he cautions that any drug would need to penetrate the brain.
TITLE: Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents
AUTHOR CONTACT:
Sabrina Diano
Yale University School of Medicine, New Haven, Connecticut, USA.
Phone: (203) 737-1216; Fax: (203) 785-4747; E-mail: sabrina.diano@yale.edu.
Craig H. Warden
University of California Davis, Davis, California, USA.
Phone: (530) 752-4187; Fax: (530) 752-3516; E-mail: chwarden@ucdavis.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=37209
ACCOMPANYING COMMENTARY
TITLE: Reduced levels of neurotransmitter-degrading enzyme PRCP promote obesity
AUTHOR CONTACT:
Richard D. Palmiter
University of Washington, Seattle, Washington, USA.
Phone: (206) 543-6064; Fax: (206) 543-0858; E-mail: palmiter@u.washington.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=40001
Journal
Journal of Clinical Investigation