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However, the potential role of NR4A1 in Hcy\u2010associated NAFLD remains elusive. We aimed to elucidate the regulation of NR4A1 and its significance in Hcy\u2010induced NAFLD. Hcy induced steatosis and elevated the expression of <jats:italic>CD36<\/jats:italic> and <jats:italic>FATP2<\/jats:italic> in HepG2 cells. Furthermore, Hcy enhanced p300 and decreased HDAC7 recruitment to the <jats:italic>NR4A1<\/jats:italic> promoter, resulting in histone H3K27 hyperacetylation and NR4A1 upregulation. Moreover, NR4A1 depletion not only mimicked but also exaggerated the effects of Hcy on steatosis, whereas NR4A1 agonist Cytosporone B (CsnB) blocked Hcy\u2010induced steatosis. In hyperhomocysteinemia (HHcy) mice, CsnB attenuated HHcy\u2010induced hepatic steatosis. Thus, Hcy transiently and rapidly induces NR4A1 expression to reduce Hcy\u2010induced steatosis.<\/jats:p>","DOI":"10.1002\/1873-3468.13384","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T04:00:42Z","timestamp":1555041642000},"page":"1061-1071","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Orphan nuclear receptor NR4A1 suppresses hyperhomocysteinemia\u2010induced hepatic steatosis <i>in\u00a0vitro<\/i> and <i>in\u00a0vivo<\/i>"],"prefix":"10.1002","volume":"593","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-6756","authenticated-orcid":false,"given":"Hongjin","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Genetics Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes Shantou University Medical College China"},{"name":"Department of Rheumatology the 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