{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:10:34Z","timestamp":1791418234350,"version":"4.3.3"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,30]]},"abstract":"\n Inactivating mutations of the pro-opiomelanocortin (POMC) gene in both mice and humans leads to hyperphagia and obesity. To further examine the mechanisms whereby POMC-deficiency leads to disordered energy homeostasis, we have generated mice lacking all POMC-derived peptides. Consistent with a previously reported model,\n Pomc<\/jats:italic>\n -\/-<\/jats:sup>\n mice were obese and hyperphagic. They also showed reduced resting oxygen consumption associated with lowered serum levels of thyroxine. Hypothalami from\n Pomc<\/jats:italic>\n -\/-<\/jats:sup>\n mice showed markedly increased expression of melanin-concentrating hormone mRNA in the lateral hypothalamus, but expression of neuropeptide Y mRNA in the arcuate nucleus was not altered. Provision of a 45% fat diet increased energy intake and body weight in both\n Pomc<\/jats:italic>\n -\/-<\/jats:sup>\n and\n Pomc<\/jats:italic>\n +\/-<\/jats:sup>\n mice. The effects of leptin on food intake and body weight were blunted in obese\n Pomc<\/jats:italic>\n -\/-<\/jats:sup>\n mice whereas nonobese\n Pomc<\/jats:italic>\n -\/-<\/jats:sup>\n mice were sensitive to leptin. Surprisingly, we found that\n Pomc<\/jats:italic>\n -\/-<\/jats:sup>\n mice maintained their acute anorectic response to peptide-YY\n 3-36<\/jats:sub>\n (PYY\n 3-36<\/jats:sub>\n ). However, 7 days of PYY\n 3-36<\/jats:sub>\n administration had no effect on cumulative food intake or body weight in wild-type or\n Pomc<\/jats:italic>\n -\/-<\/jats:sup>\n mice. Thus, POMC peptides seem to be necessary for the normal response of energy balance to high-fat feeding, but not for the acute anorectic effect of PYY\n 3-36<\/jats:sub>\n or full effects of leptin on feeding. The finding that the loss of only one copy of the\n Pomc<\/jats:italic>\n gene is sufficient to render mice susceptible to the effects of high fat feeding emphasizes the potential importance of this locus as a site for gene-environment interactions predisposing to obesity.\n <\/jats:p>","DOI":"10.1073\/pnas.0306931101","type":"journal-article","created":{"date-parts":[[2004,3,30]],"date-time":"2004-03-30T14:58:04Z","timestamp":1080658684000},"page":"4695-4700","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":326,"title":["Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY\n 3-36<\/sub>"],"prefix":"10.1073","volume":"101","author":[{"given":"B. G.","family":"Challis","sequence":"first","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. P.","family":"Coll","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. S. H.","family":"Yeo","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. B.","family":"Pinnock","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. L.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. R.","family":"Thresher","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Zahn","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Rochford","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"White","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. L.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Millington","sequence":"additional","affiliation":[{"name":"Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom; Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Paradigm Therapeutics, 214 Cambridge Science Park, Milton Road, Cambridge CB4 0WA, United Kingdom; School of Biological Sciences and Faculty of Medicine, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Oncology, University of Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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