{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:41:50Z","timestamp":1777452110323,"version":"3.51.4"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T00:00:00Z","timestamp":1553212800000},"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":[[2019,8]]},"abstract":"<jats:p>\n                    In nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate within the liver because the rates of fatty acid accrual by uptake from plasma and\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    synthesis exceed elimination by mitochondrial oxidation and secretion as very low\u2010density lipoprotein (VLDL) triglycerides. Thioesterase superfamily member 2 (Them2) is an acyl\u2010coenzyme A (CoA) thioesterase that catalyzes the hydrolysis of fatty acyl\u2010CoAs into free fatty acids plus CoASH. Them2 is highly expressed in the liver, as well as other oxidative tissues. Mice globally lacking Them2 are resistant to diet\u2010induced obesity and hepatic steatosis, and exhibit improved glucose homeostasis. These phenotypes are attributable, at least in part, to roles of Them2 in the suppression of thermogenesis in brown adipose tissue and insulin signaling in skeletal muscle. To elucidate the hepatic function of Them2, we created mice with liver\u2010specific deletion of Them2 (\n                    <jats:italic toggle=\"yes\">L\u2010Them2<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    ). Although\n                    <jats:italic toggle=\"yes\">L\u2010Them2<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice were not protected against excess weight gain, hepatic steatosis or glucose intolerance, they exhibited marked decreases in plasma triglyceride and apolipoprotein B100 concentrations. These were attributable to reduced rates of VLDL secretion owing to decreased incorporation of plasma\u2010derived fatty acids into triglycerides. The absence of hepatic steatosis in\n                    <jats:italic toggle=\"yes\">L\u2010Them2<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice fed chow was explained by compensatory increases in rates of fatty acid oxidation and by decreased\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    lipogenesis in high fat\u2013fed mice. Consistent with a role for Them2 in hepatic VLDL secretion, THEM2 levels were increased in livers of obese patients with NAFLD characterized by simple steatosis.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Them2 functions in the liver to direct fatty acids toward triglyceride synthesis for incorporation into VLDL particles. When taken together with its functions in brown adipose and muscle, these findings suggest that Them2 is a target for the management of NAFLD and dyslipidemia.\n                  <\/jats:p>","DOI":"10.1002\/hep.30411","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T11:49:08Z","timestamp":1544010548000},"page":"496-510","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":27,"title":["Thioesterase Superfamily Member 2 Promotes Hepatic VLDL Secretion by Channeling Fatty Acids Into Triglyceride Biosynthesis"],"prefix":"10.1097","volume":"70","author":[{"given":"Michele","family":"Alves\u2010Bezerra","sequence":"first","affiliation":[{"name":"Joan & Sanford I. Weill Department of Medicine,Weill Cornell Medical College,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxia","family":"Li","sequence":"additional","affiliation":[{"name":"Joan & Sanford I. Weill Department of Medicine,Weill Cornell Medical College,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Acu\u00f1a","sequence":"additional","affiliation":[{"name":"Joan & Sanford I. Weill Department of Medicine,Weill Cornell Medical College,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna A.","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Emory Integrated Lipidomics Core, Emory University,Atlanta,GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen E.","family":"Corey","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit,Massachusetts General Hospital,Boston,MA"},{"name":"Harvard Medical School,Boston,MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric A.","family":"Ortlund","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,Emory University School of Medicine,Atlanta,GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David E.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Joan & Sanford I. Weill Department of Medicine,Weill Cornell Medical College,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2019,3,22]]},"reference":[{"key":"hep30411-bib-0001-20241017","first-page":"1","article-title":"Triglyceride metabolism in the liver","volume":"8","year":"2017","journal-title":"Compr Physiol"},{"key":"hep30411-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-nutr-071813-105541","article-title":"Acyl\u2010CoA metabolism and partitioning","volume":"34","year":"2014","journal-title":"Ann Rev Nutr"},{"key":"hep30411-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.tem.2017.03.001","article-title":"Deactivating fatty acids: acyl\u2010CoA thioesterase\u2010mediated control of lipid metabolism","volume":"28","year":"2017","journal-title":"Trends Endocrinol 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History"}},{"value":"2018-11-30","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}