Orphan nuclear receptor NR4A1 suppresses hyperhomocysteinemia‐induced hepatic steatosis in vitro and in vivo
Autor: | Ting Su, Dongyang Huang, Xina Xie, Bin Liang, Meihui Huang, Xuhong Song, Hongjin Liang, Xiaolan Chang |
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Rok vydání: | 2019 |
Předmět: |
Male
Agonist medicine.medical_specialty Hyperhomocysteinemia Homocysteine medicine.drug_class CD36 Biophysics Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound Downregulation and upregulation Structural Biology Internal medicine Nonalcoholic fatty liver disease Nuclear Receptor Subfamily 4 Group A Member 1 Genetics medicine Animals Humans Molecular Biology 030304 developmental biology 0303 health sciences biology Chemistry 030302 biochemistry & molecular biology Hep G2 Cells Cell Biology medicine.disease Fatty Liver Mice Inbred C57BL Endocrinology Gene Expression Regulation Nuclear receptor biology.protein Steatosis |
Zdroj: | FEBS Letters. 593:1061-1071 |
ISSN: | 1873-3468 0014-5793 |
Popis: | 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 of CD36 and FATP2 in HepG2 cells. Furthermore, Hcy enhanced p300 and decreased HDAC7 recruitment to the NR4A1 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. |
Databáze: | OpenAIRE |
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