{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T16:27:40Z","timestamp":1770222460159,"version":"3.49.0"},"reference-count":66,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T00:00:00Z","timestamp":1466640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Leptin, an important regulator of the energy balance, acts on the brain to inhibit feeding. However, the mechanisms involved in leptin signalling have not yet been fully elucidated. Heat shock protein 90 (HSP90) is a molecular chaperone that is involved in regulating cellular homeostasis. In the present study, we investigated the possible involvement of HSP90 in leptin signal transduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>HEK293 and SH\u2010SY5Y cell lines stably transfected with the Ob\u2010Rb leptin receptor (HEK293 Ob\u2010Rb, SH\u2010SY5Y Ob\u2010Rb) were used in the present study. Phosphorylation of JAK2 and STAT3 was analysed by western blotting. An HSP90 inhibitor was administered i.c.v. into rats and their food intake was analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The knock\u2010down of HSP90 in the HEK293 Ob\u2010Rb cell line attenuated leptin\u2010induced JAK2 and STAT3 signalling. Moreover, leptin\u2010induced JAK2\/STAT3 phosphorylation was markedly attenuated by the HSP90 inhibitors geldanamycin, radicicol and novobiocin. However, these effects were not mediated through previously known factors, which are known to be involved in the development of leptin resistance, such as suppressor of cytokine signalling 3 or endoplasmic reticulum stress. The infusion of an HSP90 inhibitor into the CNS blunted the anorexigenic actions of leptin in rats (male Wister rat).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>HSP90 may be a novel factor involved in leptin\u2010mediated signalling that is linked to anorexia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13520","type":"journal-article","created":{"date-parts":[[2016,5,22]],"date-time":"2016-05-22T11:11:13Z","timestamp":1463915473000},"page":"2434-2445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Key role of heat shock protein 90 in leptin\u2010induced STAT3 activation and feeding regulation"],"prefix":"10.1111","volume":"173","author":[{"given":"Toru","family":"Hosoi","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiko","family":"Kohda","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syu","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuho","family":"Ishiguchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Kuwamura","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Akita","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Infectious Disease Control and Prevention, Institute of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Infectious Disease Control and Prevention, Institute of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13353"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.6.6774"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0162"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01388"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp041"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80062-3"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007577200"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624778"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00149-1"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.08.006"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00205-X"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242720499"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1544"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/43213"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606192200"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2572com"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079856"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90794-3"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6231"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2012.11.002"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703753200"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220077"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.09.044"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20080680"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040144"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.050070"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201303227"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0749"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0020-711X(93)90494-Y"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0530fje"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01913"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.15.5479-5489.2000"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.63051787.x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2.1.3"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003701200"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2890"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1454"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0726"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/43219"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(92)90028-5"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.12.004"},{"key":"e_1_2_11_48_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3233\/JAD-2011-102070","article-title":"Leptin induces proliferation of neuronal progenitors and neuroprotection in a mouse model of Alzheimer's disease","volume":"2","author":"P\u00e9rez\u2010Gonz\u00e1lez R","year":"2011","journal-title":"J Alzheimers Dis"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm980403y"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1767"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02941-8"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/35007534"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205935200"},{"key":"e_1_2_11_54_1","first-page":"986","article-title":"17\u2010Allylamino\u201017\u2010demethoxygeldanamycin induces the degradation of androgen receptor and HER\u20102\/neu and inhibits the growth of prostate cancer xenografts","volume":"8","author":"Solit DB","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.06.004"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/43206"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2918"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-95"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(79)90160-4"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705426200"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-129-3-1584"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0655"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00148-X"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.043"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/372425a0"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05645.x"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13520","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13520","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T10:54:33Z","timestamp":1696244073000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.13520"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,23]]},"references-count":66,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1111\/bph.13520"],"URL":"https:\/\/doi.org\/10.1111\/bph.13520","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,23]]},"assertion":[{"value":"2015-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-06-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}