{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:18:41Z","timestamp":1790165921385,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":700,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,10]]},"abstract":"\n \n \n Methionine adenosyltransferase 1A (<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n ) and glycine<\/jats:bold>\n \n N\n <\/jats:bold>\n -methyltransferase (<\/jats:bold>\n \n GNMT\n <\/jats:bold>\n ) are the primary genes involved in hepatic S-adenosylmethionine (SAMe) synthesis and degradation, respectively.<\/jats:bold>\n \n Mat1a\n <\/jats:bold>\n ablation in mice induces a decrease in hepatic SAMe, activation of lipogenesis, inhibition of triglyceride (TG) release, and steatosis.<\/jats:bold>\n \n Gnmt\n <\/jats:bold>\n -deficient mice, despite showing a large increase in hepatic SAMe, also develop steatosis. We hypothesized that as an adaptive response to hepatic SAMe accumulation, phosphatidylcholine (PC) synthesis by way of the phosphatidylethanolamine (PE)<\/jats:bold>\n \n N\n <\/jats:bold>\n -methyltransferase (PEMT) pathway is stimulated in<\/jats:bold>\n \n Gnmt\u2212\/\u2212\n \n <\/jats:bold>\n mice. We also propose that the excess PC thus generated is catabolized, leading to TG synthesis and steatosis by way of diglyceride (DG) generation. We observed that<\/jats:bold>\n \n Gnmt\u2212\/\u2212\n \n <\/jats:bold>\n mice present with normal hepatic lipogenesis and increased TG release. We also observed that the flux from PE to PC is stimulated in the liver of<\/jats:bold>\n \n Gnmt\u2212\/\u2212\n \n <\/jats:bold>\n mice and that this results in a reduction in PE content and a marked increase in DG and TG. Conversely, reduction of hepatic SAMe following the administration of a methionine-deficient diet reverted the flux from PE to PC of<\/jats:bold>\n \n Gnmt\u2212\/\u2212\n \n <\/jats:bold>\n mice to that of wildtype animals and normalized DG and TG content preventing the development of steatosis.<\/jats:bold>\n \n Gnmt\u2212\/\u2212\n \n <\/jats:bold>\n mice with an additional deletion of perilipin2, the predominant lipid droplet protein, maintain high SAMe levels, with a concurrent increased flux from PE to PC, but do not develop liver steatosis.<\/jats:bold>\n \n Conclusion\n <\/jats:bold>\n : These findings indicate that excess SAMe reroutes PE towards PC and TG synthesis and lipid sequestration. (Hepatology 2013;58:1296\u20131305)<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.26399","type":"journal-article","created":{"date-parts":[[2013,3,16]],"date-time":"2013-03-16T09:35:20Z","timestamp":1363426520000},"page":"1296-1305","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":121,"title":["Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis"],"prefix":"10.1097","volume":"58","author":[{"given":"Maite","family":"Mart\u00ednez-U\u00f1a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Varela-Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainara","family":"Cano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larraitz","family":"Fern\u00e1ndez-Ares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiara","family":"Beraza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Aurrekoetxea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibon","family":"Mart\u00ednez-Arranz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan 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