{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:51:23Z","timestamp":1791532283547,"version":"4.3.4"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,4,10]]},"abstract":"<jats:p>Ciliary Neurotrophic Factor (CNTF) was first characterized as\n a trophic factor for motor neurons in the ciliary ganglion and spinal\n cord, leading to its evaluation in humans suffering from motor neuron\n disease. In these trials, CNTF caused unexpected and substantial weight\n loss, raising concerns that it might produce cachectic-like effects.\n Countering this possibility was the suggestion that CNTF was working\n via a leptin-like mechanism to cause weight loss, based on the findings\n that CNTF acts via receptors that are not only related to leptin\n receptors, but also similarly distributed within hypothalamic nuclei\n involved in feeding. However, although CNTF mimics the ability of\n leptin to cause fat loss in mice that are obese because of genetic\n deficiency of leptin (ob\/ob mice), CNTF is also effective in\n diet-induced obesity models that are more representative of human\n obesity, and which are resistant to leptin. This discordance again\n raised the possibility that CNTF might be acting via nonleptin\n pathways, perhaps more analogous to those activated by cachectic\n cytokines. Arguing strongly against this possibility, we now show that\n CNTF can activate hypothalamic leptin-like pathways in diet-induced\n obesity models unresponsive to leptin, that CNTF improves prediabetic\n parameters in these models, and that CNTF acts very differently than\n the prototypical cachectic cytokine, IL-1. Further analyses of\n hypothalamic signaling reveals that CNTF can suppress food intake\n without triggering hunger signals or associated stress responses that\n are otherwise associated with food deprivation; thus, unlike forced\n dieting, cessation of CNTF treatment does not result in binge\n overeating and immediate rebound weight gain.<\/jats:p>","DOI":"10.1073\/pnas.061034298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"4652-4657","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":257,"title":["Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity"],"prefix":"10.1073","volume":"98","author":[{"given":"P. D.","family":"Lambert","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. D.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. W.","family":"Sleeman","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Wong","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Tan","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hijarunguru","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. L.","family":"Corcoran","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. D.","family":"Murray","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. E.","family":"Thabet","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, 777 Old Saw Mill River\r Road, Tarrytown, NY 10591; and PhytoMedica, Inc., 45\r Rockefeller Plaza, Suite 2030, New York, NY 10111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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