Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding mo...
| Main Authors: | , , , , , , , , , , , , , , |
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| 语言: | English |
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Elsevier
2024-03-01
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| 丛编: | Journal of Lipid Research |
| 主题: | |
| 在线阅读: | http://www.sciencedirect.com/science/article/pii/S002222752400018X |
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| author | Zifeng Yang Siyao Zhang Xiang Liu Rui Shu Wei Shi Weiyi Qu Dianyu Liu Zhiwei Cai Ye Wang Xu Cheng Yemao Liu Xiao-Jing Zhang Lan Bai Hongliang Li Zhi-Gang She |
| author_facet | Zifeng Yang Siyao Zhang Xiang Liu Rui Shu Wei Shi Weiyi Qu Dianyu Liu Zhiwei Cai Ye Wang Xu Cheng Yemao Liu Xiao-Jing Zhang Lan Bai Hongliang Li Zhi-Gang She |
| author_sort | Zifeng Yang |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. KDM1A, commonly known as lysine-specific histone demethylase 1, has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of KDM1A reduces lipid accumulation in primary brown adipocytes. We here investigated the role of KDM1A, one of the most important histone demethylases, in NAFLD. In this study, we observed a significant upregulation of KDM1A in NAFLD mice, monkeys, and humans compared to the control group. Based on these results, we further found that the KDM1A can exacerbate lipid accumulation and inflammation in hepatocytes and mice. Mechanistically, KDM1A exerted its effects by elevating chromatin accessibility, subsequently promoting the development of NAFLD. Furthermore, the mutation of KDM1A blunted its capability to promote the development of NAFLD. In summary, our study discovered that KDM1A exacerbates hepatic steatosis and inflammation in NAFLD via increasing chromatin accessibility, further indicating the importance of harnessing chromatin remodeling and epigenetic alteration in combating NAFLD. KDM1A might be considered as a potential therapeutic target in this regard. |
| first_indexed | 2024-03-07T20:06:18Z |
| format | Article |
| id | doaj.art-aab4230ec24d4de0bd3355956cb144b1 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-24T17:30:45Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-aab4230ec24d4de0bd3355956cb144b12024-03-28T06:36:40ZengElsevierJournal of Lipid Research0022-22752024-03-01653100513Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLDZifeng Yang0Siyao Zhang1Xiang Liu2Rui Shu3Wei Shi4Weiyi Qu5Dianyu Liu6Zhiwei Cai7Ye Wang8Xu Cheng9Yemao Liu10Xiao-Jing Zhang11Lan Bai12Hongliang Li13Zhi-Gang She14Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Institute of Model Animal, Wuhan University, Wuhan, ChinaGannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Medical University, Ganzhou, ChinaGannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Medical University, Ganzhou, ChinaInstitute of Model Animal, Wuhan University, Wuhan, China; School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaInstitute of Model Animal, Wuhan University, Wuhan, China; School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaInstitute of Model Animal, Wuhan University, Wuhan, China; Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaGannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Medical University, Ganzhou, ChinaInstitute of Model Animal, Wuhan University, Wuhan, ChinaGannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Medical University, Ganzhou, ChinaGannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Medical University, Ganzhou, ChinaDepartment of Cardiology, Huanggang Central Hospital, Huanggang, ChinaInstitute of Model Animal, Wuhan University, Wuhan, China; School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaGannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Medical University, Ganzhou, China; For correspondence: Zhi-Gang She; Hongliang Li; Lan BaiDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Institute of Model Animal, Wuhan University, Wuhan, China; Gannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Medical University, Ganzhou, China; School of Basic Medical Sciences, Wuhan University, Wuhan, China; For correspondence: Zhi-Gang She; Hongliang Li; Lan BaiDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Institute of Model Animal, Wuhan University, Wuhan, China; For correspondence: Zhi-Gang She; Hongliang Li; Lan BaiNonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. KDM1A, commonly known as lysine-specific histone demethylase 1, has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of KDM1A reduces lipid accumulation in primary brown adipocytes. We here investigated the role of KDM1A, one of the most important histone demethylases, in NAFLD. In this study, we observed a significant upregulation of KDM1A in NAFLD mice, monkeys, and humans compared to the control group. Based on these results, we further found that the KDM1A can exacerbate lipid accumulation and inflammation in hepatocytes and mice. Mechanistically, KDM1A exerted its effects by elevating chromatin accessibility, subsequently promoting the development of NAFLD. Furthermore, the mutation of KDM1A blunted its capability to promote the development of NAFLD. In summary, our study discovered that KDM1A exacerbates hepatic steatosis and inflammation in NAFLD via increasing chromatin accessibility, further indicating the importance of harnessing chromatin remodeling and epigenetic alteration in combating NAFLD. KDM1A might be considered as a potential therapeutic target in this regard.http://www.sciencedirect.com/science/article/pii/S002222752400018XNAFLDKDM1Achromatin accessibilitylipid accumulationinflammation |
| spellingShingle | Zifeng Yang Siyao Zhang Xiang Liu Rui Shu Wei Shi Weiyi Qu Dianyu Liu Zhiwei Cai Ye Wang Xu Cheng Yemao Liu Xiao-Jing Zhang Lan Bai Hongliang Li Zhi-Gang She Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD Journal of Lipid Research NAFLD KDM1A chromatin accessibility lipid accumulation inflammation |
| title | Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD |
| title_full | Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD |
| title_fullStr | Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD |
| title_full_unstemmed | Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD |
| title_short | Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD |
| title_sort | histone demethylase kdm1a promotes hepatic steatosis and inflammation by increasing chromatin accessibility in nafld |
| topic | NAFLD KDM1A chromatin accessibility lipid accumulation inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S002222752400018X |
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