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In this study, we found that the expression of key enzymes involved in Hcy metabolism is induced in the liver in response to fasting. This induction coincides with increased expression of peroxisome proliferator-activated receptor-\u03b3 coactivator (PGC)-1\u03b1, a transcriptional coactivator that regulates hepatic gluconeogenesis and mitochondrial function. PGC-1\u03b1 stimulates the expression of genes involved in Hcy metabolism in cultured primary hepatocytes as well as in the liver. Adenoviral-mediated expression of PGC-1\u03b1 in vivo leads to elevated plasma Hcy levels. In contrast, mice deficient in PGC-1\u03b1 have lower plasma Hcy concentrations. These results define a novel role for the PGC-1\u03b1 coactivator pathway in the regulation of Hcy homeostasis and suggest a potential pathogenic mechanism that contributes to hyperhomocysteinemia.<\/jats:p>","DOI":"10.1152\/ajpendo.90719.2008","type":"journal-article","created":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T21:28:29Z","timestamp":1232573309000},"page":"E543-E548","source":"Crossref","is-referenced-by-count":13,"title":["Regulation of homocysteine homeostasis through the transcriptional coactivator PGC-1\u03b1"],"prefix":"10.1152","volume":"296","author":[{"given":"Siming","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erland","family":"Arning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Vitvitsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruma","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandie D.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055227"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.1130040606"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(92)90590-4"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-5-199909070-00008"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27794"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.040"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.12.1967"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501971200"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.16.2023"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/nm1044"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10268"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030101"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.06.013"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.004"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303643200"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.013"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1038\/nature05767"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060900"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.28.061807.155438"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.1.19"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00498.2005"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.11.034"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1038\/nature03354"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1042\/bj3500685"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(91)80407-4"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00375.2003"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7374.1202"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.11.3245"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1038\/35093050"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.90719.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T15:21:59Z","timestamp":1567956119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.90719.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["10.1152\/ajpendo.90719.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.90719.2008","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1159425.619787","asserted-by":"object"}]},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3]]}}}