Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease
Objective: Hepatic miR-34a expression is elevated in diet-induced or genetically obese mice and patients with non-alcoholic steatohepatitis (NASH), yet hepatocyte miR-34a's role in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to NASH remains...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877821000892 |
| _version_ | 1818923219673939968 |
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| author | Yanyong Xu Yingdong Zhu Shuwei Hu Xiaoli Pan Fathima Cassim Bawa Helen H. Wang David Q.-H. Wang Liya Yin Yanqiao Zhang |
| author_facet | Yanyong Xu Yingdong Zhu Shuwei Hu Xiaoli Pan Fathima Cassim Bawa Helen H. Wang David Q.-H. Wang Liya Yin Yanqiao Zhang |
| author_sort | Yanyong Xu |
| collection | DOAJ |
| description | Objective: Hepatic miR-34a expression is elevated in diet-induced or genetically obese mice and patients with non-alcoholic steatohepatitis (NASH), yet hepatocyte miR-34a's role in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to NASH remains to be elucidated. Methods: Mice overexpressing or deficient in hepatocyte miR-34a and control mice were fed a diet enriched in fats, cholesterol, and fructose (HFCF) to induce NASH. C57BL/6 mice with NASH were treated with an miR-34a inhibitor or a scramble control oligo. The effect of miR-34a on the development, progression, and reversal of NAFLD was determined. Results: The hepatocyte-specific expression of miR-34a aggravated HFCF diet-induced NAFLD. In contrast, germline or adult-onset deletion of hepatocyte miR-34a attenuated the development and progression of NAFLD. In addition, pharmacological inhibition of miR-34a reversed HFCF diet-induced steatohepatitis. Mechanistically, hepatocyte miR-34a regulated the development and progression of NAFLD by inducing lipid absorption, lipogenesis, inflammation, and apoptosis but inhibiting fatty acid oxidation. Conclusions: Hepatocyte miR-34a is an important regulator in the development and progression of NAFLD. MiR-34a may be a useful target for treating NAFLD. |
| first_indexed | 2024-12-20T02:05:58Z |
| format | Article |
| id | doaj.art-c3ec0c6e17764eb18b186d2835ffbcf1 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-20T02:05:58Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-c3ec0c6e17764eb18b186d2835ffbcf12022-12-21T19:57:12ZengElsevierMolecular Metabolism2212-87782021-09-0151101244Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver diseaseYanyong Xu0Yingdong Zhu1Shuwei Hu2Xiaoli Pan3Fathima Cassim Bawa4Helen H. Wang5David Q.-H. Wang6Liya Yin7Yanqiao Zhang8Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USADepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USADepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USADepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USADepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USADepartment of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USADepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA; Corresponding author. Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA. Tel.: 330-325-6693.Objective: Hepatic miR-34a expression is elevated in diet-induced or genetically obese mice and patients with non-alcoholic steatohepatitis (NASH), yet hepatocyte miR-34a's role in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to NASH remains to be elucidated. Methods: Mice overexpressing or deficient in hepatocyte miR-34a and control mice were fed a diet enriched in fats, cholesterol, and fructose (HFCF) to induce NASH. C57BL/6 mice with NASH were treated with an miR-34a inhibitor or a scramble control oligo. The effect of miR-34a on the development, progression, and reversal of NAFLD was determined. Results: The hepatocyte-specific expression of miR-34a aggravated HFCF diet-induced NAFLD. In contrast, germline or adult-onset deletion of hepatocyte miR-34a attenuated the development and progression of NAFLD. In addition, pharmacological inhibition of miR-34a reversed HFCF diet-induced steatohepatitis. Mechanistically, hepatocyte miR-34a regulated the development and progression of NAFLD by inducing lipid absorption, lipogenesis, inflammation, and apoptosis but inhibiting fatty acid oxidation. Conclusions: Hepatocyte miR-34a is an important regulator in the development and progression of NAFLD. MiR-34a may be a useful target for treating NAFLD.http://www.sciencedirect.com/science/article/pii/S2212877821000892miR-34aNAFLDLipogenesisLipid absorptionBile acids |
| spellingShingle | Yanyong Xu Yingdong Zhu Shuwei Hu Xiaoli Pan Fathima Cassim Bawa Helen H. Wang David Q.-H. Wang Liya Yin Yanqiao Zhang Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease Molecular Metabolism miR-34a NAFLD Lipogenesis Lipid absorption Bile acids |
| title | Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease |
| title_full | Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease |
| title_fullStr | Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease |
| title_full_unstemmed | Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease |
| title_short | Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease |
| title_sort | hepatocyte mir 34a is a key regulator in the development and progression of non alcoholic fatty liver disease |
| topic | miR-34a NAFLD Lipogenesis Lipid absorption Bile acids |
| url | http://www.sciencedirect.com/science/article/pii/S2212877821000892 |
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