DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummary
Background & Aims: Nonalcoholic fatty liver disease is the most prevalent chronic liver disease and threats to human health. Gut dysbiosis caused by lipopolysaccharide (LPS) leakage has been strongly related to nonalcoholic fatty liver disease progression, although the underlying mechanisms...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X23001649 |
| _version_ | 1797630577718853632 |
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| author | Qiang Li Wenjing Wang Feifan Duan Yaju Wang Shuya Chen Kangyun Shi Yinyin Xia Xinyu Li Yu Gao Guoquan Liu |
| author_facet | Qiang Li Wenjing Wang Feifan Duan Yaju Wang Shuya Chen Kangyun Shi Yinyin Xia Xinyu Li Yu Gao Guoquan Liu |
| author_sort | Qiang Li |
| collection | DOAJ |
| description | Background & Aims: Nonalcoholic fatty liver disease is the most prevalent chronic liver disease and threats to human health. Gut dysbiosis caused by lipopolysaccharide (LPS) leakage has been strongly related to nonalcoholic fatty liver disease progression, although the underlying mechanisms remain unclear. Methods: Previous studies have shown that low-grade LPS administration to mice on a standard, low-fat chow diet is sufficient to induce symptoms of fatty liver. This study confirmed these findings and supported LPS as a lipid metabolism regulator in the liver. Results: Mechanically, LPS induced dysregulated lipid metabolism by inhibiting the expression of DNA methyltransferases 3B (DNMT3B). Genetic overexpression of DNMT3B alleviated LPS-induced lipid accumulation, whereas its knockdown increased steatosis in mice and human hepatocytes. LPS-induced lower expression of DNMT3B led to hypomethylation in promoter region of CIDEA, resulting in increased binding of SREBP-1c to its promoter and activated CIDEA expression. Hepatic interference of CIDEA reversed the effect of LPS on lipogenesis. These effects were independent of a high-fat diet or high fatty acid action. Conclusions: Overall, these findings sustain the conclusion that LPS is a lipogenic factor and could be involved in hepatic steatosis progression. |
| first_indexed | 2024-03-11T11:10:09Z |
| format | Article |
| id | doaj.art-177f22d947f6408481e9740f394c7358 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-03-11T11:10:09Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-177f22d947f6408481e9740f394c73582023-11-12T04:40:13ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2024-01-011715977DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummaryQiang Li0Wenjing Wang1Feifan Duan2Yaju Wang3Shuya Chen4Kangyun Shi5Yinyin Xia6Xinyu Li7Yu Gao8Guoquan Liu9Department of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, China; Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Anhui, China; Qiang Li, PhD, Department of Cell Biology, School of Life Science, Bengbu Medical College, Donghai Road, Anhui, China.Department of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, ChinaDepartment of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, ChinaDepartment of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, ChinaDepartment of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, ChinaDepartment of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, ChinaDepartment of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, ChinaDepartment of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, ChinaDepartment of Cell Biology, School of Life Science, Bengbu Medical College, Anhui, China; Bengbu Medical College Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Bengbu Medical College, Bengbu, ChinaAnhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Anhui, China; Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Anhui, China; Correspondence Address correspondence to: Guoquan Liu, PhD, Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Donghai Road, Anhui, China.Background & Aims: Nonalcoholic fatty liver disease is the most prevalent chronic liver disease and threats to human health. Gut dysbiosis caused by lipopolysaccharide (LPS) leakage has been strongly related to nonalcoholic fatty liver disease progression, although the underlying mechanisms remain unclear. Methods: Previous studies have shown that low-grade LPS administration to mice on a standard, low-fat chow diet is sufficient to induce symptoms of fatty liver. This study confirmed these findings and supported LPS as a lipid metabolism regulator in the liver. Results: Mechanically, LPS induced dysregulated lipid metabolism by inhibiting the expression of DNA methyltransferases 3B (DNMT3B). Genetic overexpression of DNMT3B alleviated LPS-induced lipid accumulation, whereas its knockdown increased steatosis in mice and human hepatocytes. LPS-induced lower expression of DNMT3B led to hypomethylation in promoter region of CIDEA, resulting in increased binding of SREBP-1c to its promoter and activated CIDEA expression. Hepatic interference of CIDEA reversed the effect of LPS on lipogenesis. These effects were independent of a high-fat diet or high fatty acid action. Conclusions: Overall, these findings sustain the conclusion that LPS is a lipogenic factor and could be involved in hepatic steatosis progression.http://www.sciencedirect.com/science/article/pii/S2352345X23001649Liver steatosisDNMT3BLPSCIDEADNA methylation |
| spellingShingle | Qiang Li Wenjing Wang Feifan Duan Yaju Wang Shuya Chen Kangyun Shi Yinyin Xia Xinyu Li Yu Gao Guoquan Liu DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummary Cellular and Molecular Gastroenterology and Hepatology Liver steatosis DNMT3B LPS CIDEA DNA methylation |
| title | DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummary |
| title_full | DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummary |
| title_fullStr | DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummary |
| title_full_unstemmed | DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummary |
| title_short | DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA ExpressionSummary |
| title_sort | dnmt3b alleviates liver steatosis induced by chronic low grade lps via inhibiting cidea expressionsummary |
| topic | Liver steatosis DNMT3B LPS CIDEA DNA methylation |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X23001649 |
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