{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:25:10Z","timestamp":1775841910047,"version":"3.50.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T00:00:00Z","timestamp":1546214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T00:00:00Z","timestamp":1546214400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Gastric mechanistic target of rapamycin (mTOR) signaling is inversely associated with the expression and secretion of ghrelin, a 28\u2010aa peptide hormone produced by gastric X\/A\u2010like cells. Ghrelin contributes to obesity and hepatic steatosis. We sought to control global lipid metabolism via the manipulation of gastric mTOR signaling in X\/A\u2010like cells. We established a <jats:italic toggle=\"yes\">ghrl\u2010cre<\/jats:italic> transgene in which the Cre enzyme is expressed in X\/A\u2010like cells under the control of the ghrelin\u2010promoter. <jats:italic toggle=\"yes\">mTORflox\/flox\n                           <\/jats:italic> and tuberous sclerosis 1 (<jats:italic toggle=\"yes\">TSC1)flox\/flox\n                           <\/jats:italic> mice were separately bred with <jats:italic toggle=\"yes\">ghrl\u2010cre<\/jats:italic> mice to generate <jats:italic toggle=\"yes\">mTOR\u2010ghrl\u2010cre<\/jats:italic> or <jats:italic toggle=\"yes\">TSC1\u2010ghrl\u2010cre<\/jats:italic> mice, within which mTOR signaling was suppressed or activated, respectively. Lipid metabolism in liver and adipose depots was analyzed. Under the control of the ghrelin\u2010promoter, the Cre enzyme was exclusively expressed in stomach X\/A\u2010like cells in adult animals. Knockout of mTOR in X\/A\u2010like cells increased circulating acyl\u2010ghrelin and promoted hepatic lipogenesis with effects on adipose depots. Activation of mTOR signaling by deletion of its upstream inhibitor, TSC1, decreased ghrelin expression and secretion, altering lipid metabolism as evidenced by resistance to high\u2010fat diet\u2013induced obesity and hepatic steatosis. Both ghrelin administration and injection of rapamycin, an inhibitor of mTOR, altered the phenotypes of <jats:italic toggle=\"yes\">TSC1\u2010ghrl\u2010cre<\/jats:italic> mice. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Gastric mTOR signaling in X\/A\u2010like cells contributes to organism lipid homeostasis by regulating hepatic and adipose lipid metabolism. Gastric mTOR signaling may provide an alternative strategy for intervention in lipid disorders.<\/jats:p>","DOI":"10.1002\/hep.30229","type":"journal-article","created":{"date-parts":[[2018,8,24]],"date-time":"2018-08-24T01:33:42Z","timestamp":1535074422000},"page":"860-875","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":15,"title":["mTOR Signaling in X\/A\u2010Like Cells Contributes to Lipid Homeostasis in Mice"],"prefix":"10.1097","volume":"69","author":[{"given":"Ziru","family":"Li","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences,Peking University,Beijing,China"},{"name":"Department of Surgery,University of Michigan Medical Center,Ann Arbor,MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruili","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences,Peking University,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhen","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences,Peking University,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences,Peking University,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangxiao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences,Peking University,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Mulholland","sequence":"additional","affiliation":[{"name":"Department of Surgery,University of Michigan Medical Center,Ann 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