{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T17:35:54Z","timestamp":1778261754804,"version":"3.51.4"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T00:00:00Z","timestamp":1615680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPG5J0191"],"award-info":[{"award-number":["CMRPG5J0191"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004946","name":"National Chung-Hsing University","doi-asserted-by":"publisher","award":["TCVGH\u2010NCHU\u20101097612"],"award-info":[{"award-number":["TCVGH\u2010NCHU\u20101097612"]}],"id":[{"id":"10.13039\/501100004946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Everolimus, which inhibits mTOR kinase activity and is clinically used in graft rejection treatment, may have a two\u2010sided influence on metabolic syndrome; its role in obesity and hyperglycemic in animals and humans, however, has been explored insufficiently. This study further determined how continual everolimus treatment affects glucose homeostasis and body weight control in C57BL6\/J mice with obesity. An obesity mouse model was developed by administering a high\u2010fat diet (HFD) to C57BL6\/J mice over 12\u00a0weeks. The experimental group, while continuing their HFD consumption, were administered everolimus daily for 8\u00a0weeks. Metabolic parameters, glucose tolerance, fatty liver score, endocrine profile, insulin sensitivity index (ISI), insulin resistance (IR) index, and Akt phosphorylation, GLUT4, TNF\u2010\u03b1, and IL\u20101 levels were measured in vivo. Compared with the control group, the everolimus group gained less body weight and had smaller adipocytes and lower fat pad weight; triglyceride (serum and hepatic), patatin\u2010like phospholipase domain\u2010containing 3, and fatty acid synthase levels; fatty liver scores; and glucose tolerance test values\u2014all despite consuming more food. However, the everolimus group exhibited decreased ISI and muscle Akt phosphorylation and GLUT4 expression as well as impaired glucose tolerance and serum TNF\u2010\u03b1 and IL\u20101\u03b2 levels\u2014even when insulin levels were high. In conclusion, continual everolimus treatment may lead to diabetes with glucose intolerance and IR.<\/jats:p>","DOI":"10.1002\/prp2.732","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T12:19:05Z","timestamp":1615724345000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Chronic everolimus treatment of high\u2010fat diet mice leads to a reduction in obesity but impaired glucose tolerance"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0577-3339","authenticated-orcid":false,"given":"Geng\u2010Ruei","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine National Chiayi University Chiayi Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Hsun","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Taichung Veterans General Hospital Taichung Taiwan"},{"name":"Faculty of Medicine National Yang\u2010Ming University Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao\u2010Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine National Chiayi University Chiayi Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching\u2010Feng","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Thoracic and Cardiovascular Surgery Department of Surgery Chang Gung University Chang Gung Memorial Hospital Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huang\u2010Kai","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine National Chiayi University Chiayi Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huei\u2010Jyuan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine National Chiayi University Chiayi Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"To\u2010Pang","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Show Chwan Memorial Hospital Changhua Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-010-0967-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-017-0317-0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.04.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.2526"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02866"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13168"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2640342"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.1.63-76.2006"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2017.09.009"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.08215FP"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010409"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2012.04.018"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.11.013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2009.00427.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13557"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000090393.75600.32"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000164352.65613.24"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.01063.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2008.05.011"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10061-2"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15194"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12097"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani10081423"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.08.002"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901427g"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2018.12.004"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000063934.89714.19"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.09.019"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/08860220903134555"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.2739"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2010.284"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.421552"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25071658"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i6.802"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215135"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13229"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjd.2017.10.040"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.0988"},{"key":"e_1_2_10_40_1","first-page":"495","article-title":"Long\u2010term administration of olanzapine induces adiposity and increases hepatic fatty acid desaturation protein in female C57BL\/6J mice","volume":"21","author":"Hou PH","year":"2018","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.06.003"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.08.002"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.12659\/AOT.910952"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-013-2630-y"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.03.030"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ18-0542"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13024"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0222"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101117"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/1721727X1401200213"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-016-0412-5"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2013.1135"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.04.011"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.5.1543.1543"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aab3715"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26174"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.62"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.09.004"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.732","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.732","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.732","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T04:27:59Z","timestamp":1693283279000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,14]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1002\/prp2.732"],"URL":"https:\/\/doi.org\/10.1002\/prp2.732","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,14]]},"assertion":[{"value":"2020-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00732"}}