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It is well established that genetic and gender\u2010specific variations in one\u2010carbon metabolism contribute to the vulnerability to NAFLD in humans. To examine the role of one\u2010carbon metabolism dysregulation in the pathogenesis and individual susceptibility to NAFLD, we used a \u201cpopulation\u2010based\u201d mouse model where male mice from 7 inbred were fed a choline\u2010 and folate\u2010deficient (CFD) diet for 12 wk. Strain\u2010dependent down\u2010regulation of several key one\u2010carbon metabolism genes, including methionine adenosyltransferase 1\u03b1 (\n                    <jats:italic>Mat1a<\/jats:italic>\n                    ), cystathionine\u2010\u03b2\u2010synthase (\n                    <jats:italic>Cbs<\/jats:italic>\n                    ), methylenetetrahydrofolate reductase (\n                    <jats:italic>Mthfr<\/jats:italic>\n                    ), adenosyl\u2010homocysteinase (\n                    <jats:italic>Ahcy<\/jats:italic>\n                    ), and methylenetetrahydrofolate dehydrogenase 1 (\n                    <jats:italic>Mthfd1<\/jats:italic>\n                    ), was observed. These changes were strongly associated with interstrain variability in liver injury (steatosis, necrosis, inflammation, and activation of fibrogenesis) and hyperhomocysteinemia. Mechanistically, the decreased expression of\n                    <jats:italic>Mat1a, Ahcy<\/jats:italic>\n                    , and\n                    <jats:italic>Mthfd1<\/jats:italic>\n                    was linked to a reduced level and promoter binding of transcription factor CCAAT\/enhancer binding protein \u03b2 (CEBP\u03b2), which directly regulates their transcription. The strain specificity of diet\u2010induced dysregulation of one\u2010carbon metabolism suggests that interstrain variation in the regulation of one\u2010carbon metabolism may contribute to the differential vulnerability to NFLD and that correcting the imbalance may be considered as preventive and treatment strategies for NAFLD.\u2014Pogribny, I. P., Kutanzi, K., Melnyk, S., de Conti, A., Tryndyak, V., Montgomery, B., Pogribna, M., Muskhelishvili, L., Latendresse, J. R., James, S. J., Beland, F. A., Rusyn, I. Strain\u2010dependent dysregulation of one\u2010carbon metabolism in male mice is associated with choline\u2010 and folate\u2010deficient diet\u2010induced liver injury.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 2233\u20132243 (2013).\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.12-227116","type":"journal-article","created":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T00:30:06Z","timestamp":1361838606000},"page":"2233-2243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Strain\u2010dependent dysregulation of one\u2010carbon metabolism in male mice is associated with choline\u2010 and folate\u2010deficient diet\u2010induced liver injury"],"prefix":"10.1096","volume":"27","author":[{"given":"Igor P.","family":"Pogribny","sequence":"first","affiliation":[{"name":"Division of Biochemical Toxicology U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristy","family":"Kutanzi","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stepan","family":"Melnyk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"de Conti","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volodymyr","family":"Tryndyak","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Pogribna","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Levan","family":"Muskhelishvili","sequence":"additional","affiliation":[{"name":"Toxicologic Pathology Associates, National Center for Toxicological Research U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Latendresse","sequence":"additional","affiliation":[{"name":"Toxicologic Pathology Associates, National Center for Toxicological Research U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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