LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling
LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD...
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eLife Sciences Publications Ltd
2024-10-01
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| Online Access: | https://elifesciences.org/articles/96988 |
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| author | Xianghong Xie Mingyue Gao Wei Zhao Chunmei Li Weihong Zhang Jiahui Yang Yinliang Zhang Enhui Chen Yanfang Guo Zeyu Guo Minglong Zhang Ebenezeri Erasto Ngowi Heping Wang Xiaoman Wang Yinghan Zhu Yiting Wang Xiaolu Li Hong Yao Li Yan Fude Fang Meixia Li Aijun Qiao Xiaojun Liu |
| author_facet | Xianghong Xie Mingyue Gao Wei Zhao Chunmei Li Weihong Zhang Jiahui Yang Yinliang Zhang Enhui Chen Yanfang Guo Zeyu Guo Minglong Zhang Ebenezeri Erasto Ngowi Heping Wang Xiaoman Wang Yinghan Zhu Yiting Wang Xiaolu Li Hong Yao Li Yan Fude Fang Meixia Li Aijun Qiao Xiaojun Liu |
| author_sort | Xianghong Xie |
| collection | DOAJ |
| description | LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD. |
| format | Article |
| id | doaj-art-fb1fdb9a0fbb4456a2811b372765b02f |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-fb1fdb9a0fbb4456a2811b372765b02f2025-08-20T02:09:45ZengeLife Sciences Publications LtdeLife2050-084X2024-10-011310.7554/eLife.96988LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signalingXianghong Xie0https://orcid.org/0009-0001-3481-469XMingyue Gao1Wei Zhao2Chunmei Li3Weihong Zhang4Jiahui Yang5Yinliang Zhang6Enhui Chen7Yanfang Guo8Zeyu Guo9Minglong Zhang10Ebenezeri Erasto Ngowi11Heping Wang12https://orcid.org/0000-0002-0153-478XXiaoman Wang13Yinghan Zhu14Yiting Wang15Xiaolu Li16Hong Yao17Li Yan18Fude Fang19Meixia Li20https://orcid.org/0000-0001-9992-3275Aijun Qiao21https://orcid.org/0000-0001-7545-3395Xiaojun Liu22https://orcid.org/0000-0003-4672-8569Department of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Microbiology and Immunology, Shanxi Medical University, Taiyuan, ChinaDepartment of Microbiology and Immunology, Shanxi Medical University, Taiyuan, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Pathophysiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Pathophysiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Pathophysiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Microbiology and Immunology, Shanxi Medical University, Taiyuan, ChinaDepartment of Pathophysiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaState Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, ChinaDepartment of Biochemistry & Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, ChinaLncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD.https://elifesciences.org/articles/96988metabolic dysfunction-associated fatty liver diseaseSnhg3PPARγ |
| spellingShingle | Xianghong Xie Mingyue Gao Wei Zhao Chunmei Li Weihong Zhang Jiahui Yang Yinliang Zhang Enhui Chen Yanfang Guo Zeyu Guo Minglong Zhang Ebenezeri Erasto Ngowi Heping Wang Xiaoman Wang Yinghan Zhu Yiting Wang Xiaolu Li Hong Yao Li Yan Fude Fang Meixia Li Aijun Qiao Xiaojun Liu LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling eLife metabolic dysfunction-associated fatty liver disease Snhg3 PPARγ |
| title | LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling |
| title_full | LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling |
| title_fullStr | LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling |
| title_full_unstemmed | LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling |
| title_short | LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling |
| title_sort | lncrna snhg3 aggravates hepatic steatosis via pparγ signaling |
| topic | metabolic dysfunction-associated fatty liver disease Snhg3 PPARγ |
| url | https://elifesciences.org/articles/96988 |
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