Orphan nuclear receptor NR4A1 suppresses hyperhomocysteinemia ‐induced hepatic steatosis in vitro and in vivo

Homocysteine (Hcy) is associated with nonalcoholic fatty liver disease (NAFLD). orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is involved in hepatic lipid metabolism. However, the potential role of NR4A1 in Hcy ‐associated NAFLD remains elusive. We aimed to elucidate the regulation of NR4A1 and its significance in Hcy‐induced NAFLD. Hcy induced steatosis and elevated the expression ofCD36 andFATP2 in HepG2 cells. Furthermore, Hcy enhanced p300 and decreased HDAC7 recruitment to theNR4A1 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 ‐induced steatosis. In hyperhomocysteinemia (HHcy) mice, CsnB attenuated HHcy‐induced hepatic steatosis. Thus, Hcy transiently and rapidly induces NR4A1 expression to reduce Hcy‐induced steatosis.

Source: FEBS Letters - April 21, 2019 Category: Biochemistry Authors: Hongjin Liang, Xina Xie, Xuhong Song, Meihui Huang, Ting Su, Xiaolan Chang, Bin Liang, Dongyang Huang Tags: Research Letter Source Type: research