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The underlying mechanism is not fully characterized. We aimed to clarify the role of mechanistic target of rapamycin (mTOR) signaling in hepatic ischemia\/reperfusion injury (HIRI) in normal and steatotic liver using\n                    <jats:italic>\n                      Alb\u2010TSC1\n                      <jats:sup>\u2012<\/jats:sup>\n                      \/\n                      <jats:sup>\u2012<\/jats:sup>\n                    <\/jats:italic>\n                    (AT) and\n                    <jats:italic>\n                      Alb\u2010mTOR\n                      <jats:sup>\u2012<\/jats:sup>\n                      \/\n                      <jats:sup>\u2012<\/jats:sup>\n                    <\/jats:italic>\n                    (Am) transgenic mice. Steatotic liver induced by high\u2010fat diet was more vulnerable to IRI. Activation of hepatic mTOR in AT mice decreased lipid accumulation attenuated HIRI as measured by terminal deoxynucleotidyl transferase dUTP nick\u2010end labeling (TUNEL) staining, circulating levels of alanine aminotransferase and lactate dehydrogenase, and inflammatory mediators such as monocyte chemoattractant protein 1 (MCP\u20101), TNF\u2010\u03b1, and IL\u20106 and hepatic cleaved caspase 3 in mice fed either a normal chow diet or a high\u2010fat diet. The effects of mTOR activation on hepatic cleaved caspase 3 were reversed by rapamycin, an inhibitor of mTOR signaling. Inhibition of hepatic mTOR in Am mice increased hepatic lipid deposition and HIRI. The increment in hepatic susceptibility to IRI was significantly attenuated by pretreatment with IKK\u03b2 inhibitor. Further, suppression of mTOR facilitated nuclear translocation of NF\u2010kB p65. In conclusion, our study suggests that mTOR activity in hepatocytes decreases hepatic vulnerability to injury through a mechanism dependent on NF\u2010\u03baB proinflammatory cytokine signaling pathway in both normal and steatotic liver.\u2014Li, Z., Zhang, J., Mulholland, M., Zhang, W. mTOR activation protects liver from ischemia\/ reperfusion\u2010induced injury through NF\u2010\u03baB pathway. FASEB J. 31, 3018\u20133026 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201601278r","type":"journal-article","created":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T20:50:29Z","timestamp":1490820629000},"page":"3018-3026","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["mTOR activation protects liver from ischemia\/reperfusion\u2010induced injury through NF\u2010\u03baB pathway"],"prefix":"10.1096","volume":"31","author":[{"given":"Ziru","family":"Li","sequence":"first","affiliation":[{"name":"Department of Surgery University of Michigan Medical Center Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Medical Center Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mulholland","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Medical Center Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Medical Center Ann Arbor Michigan USA"},{"name":"Department of Physiology and Pathophysiology Peking University Health Science Center Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-12933"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0350236"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.016"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106148"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1183"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02866"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1324"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.7356"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.03.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2509-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61248"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.365544"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0117000","article-title":"Livers with constitutive mTORC1 activity resist steatosis independent of feedback suppression of Akt","volume":"10","author":"Kenerson H. 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