{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:53:30Z","timestamp":1790880810225,"version":"4.1.0"},"reference-count":17,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:p>Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic neuropeptide synthesized in the hypothalamus. A Leu34Phe missense mutation in proCART has been found in an obese family in humans. Here we show that humans bearing the Leu34Phe mutation in proCART have severely diminished levels of bioactive CART, but elevated amounts of partially processed proCART in their serum. Expression of wild-type proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing to bioactive CART. However, expressed Leu34Phe proCART was missorted, poorly processed, and secreted constitutively. The defective intracellular sorting of Leu34Phe proCART would account for the reduced levels of bioactive CART in affected humans. These results suggest that the obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART.<\/jats:p>","DOI":"10.1210\/en.2005-0812","type":"journal-article","created":{"date-parts":[[2005,10,7]],"date-time":"2005-10-07T00:24:19Z","timestamp":1128644659000},"page":"39-43","source":"Crossref","is-referenced-by-count":38,"title":["The Leu34Phe ProCART Mutation Leads to Cocaine- and Amphetamine-Regulated Transcript (CART) Deficiency: A Possible Cause for Obesity in Humans"],"prefix":"10.1210","volume":"147","author":[{"given":"Tulin","family":"Yanik","sequence":"first","affiliation":[{"name":"Section on Cellular Neurobiology (T.Y., Y.P.L.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldina","family":"Dominguez","sequence":"first","affiliation":[{"name":"Yerkes National Primate Center of Emory University (G.D., M.J.K.), Atlanta, Georgia 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Kuhar","sequence":"first","affiliation":[{"name":"Yerkes National Primate Center of Emory University (G.D., M.J.K.), Atlanta, Georgia 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele M.","family":"Del Giudice","sequence":"first","affiliation":[{"name":"Dipartimento di Pediatria (E.M.D.G.), Seconda Universita di Napoli, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. Peng","family":"Loh","sequence":"first","affiliation":[{"name":"Section on Cellular Neurobiology (T.Y., Y.P.L.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612384430300_R1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/35007534","article-title":"Central nervous system control of food intake.","volume":"404","author":"Schwartz","year":"2000","journal-title":"Nature"},{"key":"2020071612384430300_R2","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.tem.2004.09.010","article-title":"CART in feeding and obesity.","volume":"15","author":"Hunter","year":"2004","journal-title":"Trends Endrocrinol Metab"},{"key":"2020071612384430300_R3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1471-2156-6-19","article-title":"Analysis of sequence variability in the CART gene in relation to 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