{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:17:48Z","timestamp":1792675068907,"version":"4.5.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,6,26]]},"abstract":"<jats:p>\n                    Circulating levels of the cytokine interleukin 18 (IL-18) are elevated in obesity. Here, we show that administration of IL-18 suppresses appetite, feed efficiency, and weight regain in food-deprived male and female C57BL\/6J mice. Intraperitoneal vs. intracerebroventricular routes of IL-18 administration had similar potency and did not promote formation of a conditioned taste aversion (malaise-like behavior). Mice partially (\n                    <jats:italic>Il18<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    ) or totally (\n                    <jats:italic>Il18<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) deficient in IL-18 were hyperphagic by young adulthood, with null mutants then becoming overweight by the fifth month of life. Adult\n                    <jats:italic>Il18<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice gained 2- to 3-fold more weight than WT mice per unit energy consumed of low- or high-fat diet. Indirect calorimetry revealed reduced energy expenditure in female\n                    <jats:italic>Il18<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and increased respiratory exchange ratios [volume of carbon dioxide production (VCO\n                    <jats:sub>2<\/jats:sub>\n                    )\/volume of oxygen consumption (VO\n                    <jats:sub>2<\/jats:sub>\n                    )] in mutants of both sexes. Hyperphagia continued in maturity, with overeating greatest during the mid- to late-dark cycle. Relative white fat-pad mass of\n                    <jats:italic>Il18<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was \u22482- to 3-fold greater than that of WT, with gonadal, mesenteric, and inguinal depots growing most. The data suggest that endogenous IL-18 signaling modulates food intake, metabolism, and adiposity during adulthood and might be a central or peripheral pharmacological target for controlling energy homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0611523104","type":"journal-article","created":{"date-parts":[[2007,6,19]],"date-time":"2007-06-19T23:09:05Z","timestamp":1182294545000},"page":"11097-11102","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":157,"title":["Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency"],"prefix":"10.1073","volume":"104","author":[{"given":"Eric P.","family":"Zorrilla","sequence":"first","affiliation":[{"name":"*Harold L. Dorris Neurological Research Institute,"},{"name":"Committee on the Neurobiology of Addictive Disorders, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Sanchez-Alavez","sequence":"additional","affiliation":[{"name":"*Harold L. Dorris Neurological Research Institute,"},{"name":"Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuei","family":"Sugama","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Brennan","sequence":"additional","affiliation":[{"name":"*Harold L. Dorris Neurological Research Institute,"},{"name":"Committee on the Neurobiology of Addictive Disorders, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosette","family":"Fernandez","sequence":"additional","affiliation":[{"name":"*Harold L. Dorris Neurological Research Institute,"},{"name":"Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Bartfai","sequence":"additional","affiliation":[{"name":"*Harold L. Dorris Neurological Research Institute,"},{"name":"Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Conti","sequence":"additional","affiliation":[{"name":"*Harold L. Dorris Neurological Research Institute,"},{"name":"Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,6,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0106-62"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/378088a0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/83.2.447S"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.41.25737"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.45.29445"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5297.206"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.8.8781"},{"key":"e_1_3_4_8_2","first-page":"29","volume":"60","author":"Olusi SO","year":"2003","unstructured":"SO Olusi, A Al Awadhi, M Abraham Horm Res 60, 29\u201333 (2003).","journal-title":"Horm Res"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000163843.70369.12"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(06)74018-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1415"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.14.1799"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1381\/096089206777346763"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000034509.14906.AE"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/78.6.1135"},{"key":"e_1_3_4_16_2","volume-title":"The Fire of Life: An Introduction to Animal Energetics","author":"Kleiber M","year":"1975","unstructured":"M Kleiber The Fire of Life: An Introduction to Animal Energetics (Krieger, New York, 1975)."},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.04.008"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.1.01897"},{"key":"e_1_3_4_19_2","first-page":"R830","volume":"270","author":"Lancel M","year":"1996","unstructured":"M Lancel, S Mathias, J Faulhaber, T Schiffelholz Am J Physiol 270, R830\u2013R837 (1996).","journal-title":"Am J Physiol"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb51729.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.86.2.517"},{"key":"e_1_3_4_22_2","first-page":"662","volume":"11","author":"Arsenijevic D","year":"2000","unstructured":"D Arsenijevic, I Garcia, C Vesin, D Vesin, Y Arsenijevic, J Seydoux, L Girardier, B Ryffel, A Dulloo, D Richard Eur Cytokine Netw 11, 662\u2013668 (2000).","journal-title":"Eur Cytokine Netw"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb05827.x"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.3.R828"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(03)00440-3"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.3.C1007"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114145"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.4.2035"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6287"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.11.1579"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.domaniend.2005.07.008"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.12.009"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000389"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(99)00034-0"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03363-2"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1304"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.12.3503"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0102-75"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.04.06.db05-1250"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624777"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81294-5"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0465"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01388"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80543-9"},{"key":"e_1_3_4_45_2","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos G","year":"2001","unstructured":"G Paxinos, KBJ Franklin The Mouse Brain in Stereotaxic Coordinates (Elsevier, New York, 2001)."},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605376103"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0611523104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:45:45Z","timestamp":1649778345000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0611523104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6,26]]},"references-count":46,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2007,6,26]]}},"alternative-id":["10.1073\/pnas.0611523104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0611523104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6,26]]},"assertion":[{"value":"2006-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}