{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:22:54Z","timestamp":1792480974922,"version":"4.5.0"},"reference-count":21,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100006108","name":"HHS | NIH | National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002537"],"award-info":[{"award-number":["UL1TR002537"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL084207"],"award-info":[{"award-number":["HL084207"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX004249"],"award-info":[{"award-number":["BX004249"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:p> The mechanistic target of rapamycin complex 1 (mTORC1) signaling complex is emerging as a critical regulator of cardiovascular function with alterations in this pathway implicated in cardiovascular diseases. In this study, we used animal models and human tissues to examine the role of vascular mTORC1 signaling in the endothelial dysfunction associated with obesity. In mice, obesity induced by high-fat\/high-sucrose diet feeding for \u223c2\u2009mo resulted in aortic endothelial dysfunction without appreciable changes in vascular mTORC1 signaling. On the other hand, chronic high-fat diet feeding (45% or 60% kcal: \u223c9\u2009mo) in mice resulted in endothelial dysfunction associated with elevated vascular mTORC1 signaling. Endothelial cells and visceral adipose vessels isolated from obese humans display a trend toward elevated mTORC1 signaling. Surprisingly, genetic disruption of endothelial mTORC1 signaling through constitutive or tamoxifen inducible deletion of endothelial Raptor (critical subunit of mTORC1) did not prevent or rescue the endothelial dysfunction associated with high-fat diet feeding in mice. Endothelial mTORC1 deficiency also failed to reverse the endothelial dysfunction evoked by a high-fat\/high-sucrose diet in mice. Taken together, these data show increased vascular mTORC1 signaling in obesity, but this vascular mTORC1 activation appears not to be required for the development of endothelial impairment in obesity. <\/jats:p>","DOI":"10.1152\/ajpregu.00113.2021","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T12:40:22Z","timestamp":1625056822000},"page":"R228-R237","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Vascular effects of disrupting endothelial mTORC1 signaling in obesity"],"prefix":"10.1152","volume":"321","author":[{"given":"John J.","family":"Reho","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng-Fu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa"},{"name":"Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-7492","authenticated-orcid":true,"given":"Andreas M.","family":"Beyer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Wegman-Points","sequence":"additional","affiliation":[{"name":"Department of Health and Human Physiology, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7499-080X","authenticated-orcid":true,"given":"Gary L.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa"},{"name":"Department of Health and Human Physiology, University of Iowa, Iowa City, Iowa"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5136-6748","authenticated-orcid":true,"given":"Kamal","family":"Rahmouni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa"},{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa"},{"name":"Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa"},{"name":"Iowa City Veterans Affairs Health Care System, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.004"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1212704"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15058"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302022"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000257914.80918.72"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.14708"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.12834"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.09.003"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.0106"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01744"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32835ecbe5"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00465.2014"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.010662"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1042\/CS20170219"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00155.2015"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.001366"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00336.2015"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314944"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1726078"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/569654"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000973"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00113.2021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T14:18:40Z","timestamp":1627913920000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpregu.00113.2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,1]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,8,1]]}},"alternative-id":["10.1152\/ajpregu.00113.2021"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00113.2021","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,1]]},"assertion":[{"value":"2021-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}