{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:20:39Z","timestamp":1790839239798,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1735,"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":[[2010,12]]},"abstract":"\n Abstract<\/jats:title>\n \n Very low-density lipoprotein (VLDL) secretion provides a mechanism to export triglycerides (TG) from the liver to peripheral tissues, maintaining lipid homeostasis. In nonalcoholic fatty liver disease (NAFLD), VLDL secretion disturbances are unclear. Methionine adenosyltransferase (MAT) is responsible for<\/jats:bold>\n \n S\n <\/jats:bold>\n -adenosylmethionine (SAMe) synthesis and MAT I and III are the products of the<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n gene. Deficient MAT I and III activities and SAMe content in the liver have been associated with NAFLD, but whether<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n is required for normal VLDL assembly remains unknown. We investigated the role of<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n on VLDL assembly in two metabolic contexts: in 3-month-old<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n -knockout mice (3-KO), with no signs of liver injury, and in 8-month-old<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n -knockout mice (8-KO), harboring nonalcoholic steatohepatitis. In 3-KO mouse liver, there is a potent effect of<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n deletion on lipid handling, decreasing mobilization of TG stores, TG secretion in VLDL and phosphatidylcholine synthesis via phosphatidylethanolamine<\/jats:bold>\n \n N\n <\/jats:bold>\n -methyltransferase.<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n deletion also increased VLDL\u2013 apolipoprotein B secretion, leading to small, lipid-poor VLDL particles. Administration of SAMe to 3-KO mice for 7 days recovered crucial altered processes in VLDL assembly and features of the secreted lipoproteins. The unfolded protein response was activated in 8-KO mouse liver, in which TG accumulated and the phosphatidylcholine-to-phosphatidylethanolamine ratio was reduced in the endoplasmic reticulum, whereas secretion of TG and apolipoprotein B in VLDL was increased and the VLDL physical characteristics resembled that in 3-KO mice.<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n deletion also altered plasma lipid homeostasis, with an increase in lipid transport in low-density lipoprotein subclasses and decrease in high-density lipoprotein subclasses.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n \n MAT1A\n <\/jats:bold>\n is required for normal VLDL assembly and plasma lipid homeostasis in mice. Impaired VLDL synthesis, mainly due to SAMe deficiency, contributes to NAFLD development in<\/jats:bold>\n \n MAT1A\n <\/jats:bold>\n -KO mice. (Hepatology 2011<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.24607","type":"journal-article","created":{"date-parts":[[2011,8,11]],"date-time":"2011-08-11T14:31:14Z","timestamp":1313073074000},"page":"1975-1986","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":88,"title":["Methionine adenosyltransferase 1A gene deletion disrupts hepatic very low-density lipoprotein assembly in mice"],"prefix":"10.1097","volume":"54","author":[{"given":"Ainara","family":"Cano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xabier","family":"Buqu\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maite","family":"Mart\u00ednez-U\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Aurrekoetxea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Menor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan L.","family":"Garc\u00eda-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly C.","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz M.","family":"Mart\u00ednez-Chantar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Mato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Ochoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Aspichueta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-11-20250207","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1743-7075-7-35","article-title":"Recent progress in understanding protein and lipid factors affecting hepatic VLDL assembly and secretion.","volume":"7","author":"Sundaram","year":"2010","journal-title":"Nutr Metab (Lond)"},{"key":"R2-11-20250207","doi-asserted-by":"crossref","first-page":"772780","DOI":"10.1002\/hep.23094","article-title":"Dysfunctional verylowdensity lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis.","volume":"50","author":"Fujita","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R3-11-20250207","doi-asserted-by":"crossref","first-page":"20382044","DOI":"10.1194\/jlr.M800248-JLR200","article-title":"Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice.","volume":"49","author":"Minehira","year":"2008","journal-title":"J Lipid Res"},{"key":"R4-11-20250207","doi-asserted-by":"crossref","first-page":"679689","DOI":"10.1002\/hep.23280","article-title":"Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications.","volume":"51","author":"Fabbrini","year":"2010","journal-title":"HEPATOLOGY"},{"key":"R5-11-20250207","first-page":"2529","article-title":"Alterations in fatty acid kinetics in obese adolescents with increased intrahepatic triglyceride content.","volume":"17","author":"Fabbrini","year":"2009","journal-title":"Obesity Silver Spring"},{"key":"R6-11-20250207","doi-asserted-by":"crossref","first-page":"1639416402","DOI":"10.1016\/S0021-9258(18)49269-1","article-title":"Intrahepatic assembly of very low density lipoproteins. 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