{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:32:25Z","timestamp":1787315545334,"version":"build-2736575974"},"reference-count":26,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:p>Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. A common physiological response to obesity is hypertension, which induces cardiac remodeling and hypertrophy. Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification O-linked-\u03b2- N-acetylglucosamine ( O-GlcNAc) to proteins by O-GlcNAc transferase (OGT). OGT and O-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. Therefore, we investigated the interactions between O-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST\/mammalian switch-independent 3A\/histone deacetylase (HDAC). Five-week-old male C57BL\/6 mice were fed a Western ( n = 12) or control diet ( n = 12) for 2 wk to examine the early hypertrophic response. Western diet-fed mice exhibited fasting hyperglycemia and increased body weight ( P &lt; 0.05). As expected for this short duration of feeding, cardiac hypertrophy was not yet evident. We found that REST is O-GlcNAcylated and physically interacts with OGT in mouse hearts. Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal \u03b1-actin. Transcript levels of HDAC2 and cardiac \u03b1-actin were decreased in Western diet hearts. These data suggest that REST coordinates regulation of diet-induced hypertrophy at the level of chromatin.<\/jats:p>","DOI":"10.1152\/ajpregu.00253.2013","type":"journal-article","created":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T21:36:23Z","timestamp":1392240983000},"page":"R519-R526","source":"Crossref","is-referenced-by-count":11,"title":["Consuming a Western diet for two weeks suppresses fetal genes in mouse hearts"],"prefix":"10.1152","volume":"306","author":[{"given":"Heidi M.","family":"Medford","sequence":"first","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, Washington State University, Spokane, Washington; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Cox","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, Washington State University, Spokane, Washington; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey E.","family":"Miller","sequence":"additional","affiliation":[{"name":"Section of Clinical Pharmacology, College of Pharmacy, Washington State University, Spokane, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Section of Clinical Pharmacology, College of Pharmacy, Washington State University, Spokane, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.02.020"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00269-07"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/414813a"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.258426"},{"key":"B5","first-page":"151","volume":"6","author":"Chavali V","year":"2013","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1286905"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00422.2006"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.4868"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.12R04CP"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.6.2085-2097.2001"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg601"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00337.2010"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwj078"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0386"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-010-0699-8"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.06.011"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.04.030"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00135.2013"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009023107"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707328200"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nm1552"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070392"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00810-3"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00861-9"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-1-r9"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00253.2013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T13:23:06Z","timestamp":1567948986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00253.2013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,15]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,4,15]]}},"alternative-id":["10.1152\/ajpregu.00253.2013"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00253.2013","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,15]]}}}